Thomas "Tommy" Pickles (voiced by E.G. Daily): Tommy is an award winning junior filmmaker. He is also considered the leader of his group of friends. Tommy is also the show's main protagonist, close to his brother, and even helps out his older cousin Angelica.
Dylan Prescott "Dil" Pickles (voiced by Tara Strong): Dil is Tommy's younger brother. An inventor like his father, Dil is also an unusual boy. He often wears a distinctive purple and orange Sherpa Hat. Dil also likes to embrace many other cultures. He's a caring person who would do anything for his friends. He looks up to Tommy a lot, and sometimes Tommy is annoyed and wants space from Dil. When Tommy was secrectly filming his friends, it was revealed that the possible reason behind Dil's oddness is the fact Phil and Lil dropped him on his head as a baby. Seen when the rest of the group market his odd ideas, Dil becomes increasingly normal, either due to the lack of sleep or the piling up stress of having to actually come up with new ideas repeatedly.
Angelica Pickles (voiced by Cheryl Chase): Angelica is Tommy and Dil's older cousin. She is a typical preteen girl, who likes fashion and music. She also has good business skills like her mom, to whom she is very similar in looks. She still bosses other people around but is not as bad as when she was a child. Later revealed in the series is she still cares for her Cynthia doll, when it is accidentally disposed of by her mother when redecorating her room.
Kimi Finster (voiced by Dionne Quan): Kimi is Chuckie's young step-sister. Her mom and Chuckie's dad met in Paris. She is also Lil's best friend. Of Japanese origin, Kimi embraces her heritage. And like her best friend, she is also into boys. However, Chuckie is very protective of her. She also is the smartest of the group of friends. Every adventure they have, Kimi is the one with the brains, even in the original Rugrats.
Phil and Lil DeVille (voiced by Kath Soucie): Phil is still very close to his twin sister, Lil. He is often considered "gross", due to his love of anything smelly. A big soccer fan, he isn't very good at playing the sport, although he is often picked for the school team. Lil is into shopping and boys and is into soccer and can play the sport better than her brother can. Phil also has a brief romance with Lil's friend, Wally. Although the twins now have differing personalities, they're still very close including the typical sibling rivalry.
Susie Carmichael (voiced by Cree Summer): Susie is possibly the only who could be considered am actual friend to Angelica. Because Susie has a great singing talent, Angelica is often jealous of her. They will often compete against each other. Susie, like (Kimi), is also seen as an intelligent girl. Her strict family and good upbringing often make her seem like a goody two shoes. She's best friends with Kimi.
Harold Frumkin (voiced by Pat Musick): Harold is good friends with Angelica and Susie. Harold is actually in love with Angelica and often does things for her, like carrying her backpack and books. He also had a brief spell as an internet advice giver. It is also clear that he has a lisp. He's like Dil Pickles. 
Savannah Violeta Shane (voiced by Shayna Fox): She is the most popular girl in school, whom Angelica Pickles is jealous of, but very often, Savannah is jealous of Angelica as well. She will often compete with Angelica, because she knows there is no chance she will lose. She is characterized by her pink tank top, jean capris and black hi-top sneakers with purple laces. She's like Kimi Finster.
Brianna Penelope (voiced by Candi Milo): An enemy of Angelica and one of Savannah's closest friends.
Celestine Winona "Chelsea" Koyano (voiced by Jennifer Aquino): A close friend of Savannah and Brianna.
Nicole Boscarelli (voiced by Lizzie Murray): She is the girl at school that Chuckie Finster has a crush on. However, she only considers Chuckie to be a friend. She is characterized by her pink shirt, jeans and purple clogs. She's like Phil and Lil DeVille and Angelica Pickles.
Sean Butler (voiced by Pamela Fiona Segall Adlon): One of the most popular boys in school. Angelica has a crush on him. He is often seen hanging with Savannah. Although, he's also considered a friend by Dil, he also had a brief spell as Tommy's friend.
Justin Rogers (voiced by Candi Milo): Sean's best friend and right hand man.
Zason Ivander Maximillian Theodore "Z" Melton (voiced by Cara Delizia/Cara Harvey/Cara LeJuene): The school's bad boy and one of Kimi's closest friends. In fact, she has had a crush on him since the day they met. He is characterized by his green spiky hair.
Olivia Pickles; (voiced by Lara Jill Miller): A girl Tommy meets on vacation in the episode "Fear of Falling". Olivia becomes Tommy's first love interest and she eventually provides him with his first kiss. She is like Angelica Pickles.
Madelyn "Wally" Ramon (voiced by Jessica DiCicco): A good friend of Lil's, she is the school soccer team's captain. She was also briefly Phil's girlfriend. Phil and Lil remained friends with Wally after she broke up with Phil.
Trevor Horne (voiced by Cameron Bowen): The new kid in school who tries to win instant friends by copying Tommy's image.
Lil Q (Parody of Lil Romeo) (voiced by special guest star Lil Romeo): A strange kid, who quickly becomes one of Dil's friends. Every Valentine's Day he seems to make people fall in love. He only made one appearance in the first season episode It's Cupid, Stupid.
Francine Garcia (voiced by Philece Sampler): After being cut from a one of Tommy's films, she bullies him in the episode Fools Rush In. However, after Tommy apologizes, she becomes Tommy's friend.
Bernadette Marcus-Allcroft (voiced by Crystal Scales): a one-off character from the episode Thief Encounter. Four-year-old Bernadette is mentored by Angelica and she is exactly how Angelica used to be at that age.
Bean Mattson (voiced by Laraine Newman): The kids met Bean during the finale of the first season, Interview with a Campfire. He became a close friend of Dil in particular and is known to be a quiet person. He later turned out to be the Ghost of a missing settler.
Izzy: He is never seen on screen because he was Dil's imaginary alien friend. However, after Izzy became the most popular kid in school. Dil decided he didn't want to share him anymore. In the auditorium scene, at the end of the episode, when everybody leaves, all of the chairs are flipped up, except for one, hinting to his existence.
Chetwyn Horne (voiced by Grey DeLisle): The class nerd from Tommy's class. Tommy and Chuckie ask him to fix Pangborn's digital organizer in the episode Saving Cynthia.
Troy Banks (voiced by Ogie Banks III): A wannabe actor who tries to help Tommy get his rep back in the episode Fools Rush In.
Brett Jenks (voiced by Jennifer Hale): A one-off character from the episode Coup DeVille whom Lil has a crush on.
Diane DeLongis (voiced by Jennifer Hale): A one-off character from the episode Coup DeVille whom Lil briefly befriends. She is like Susie Carmichael.
Leslie Myers (voiced by Kate Higgins): A one-off character from the episode Coup DeVille whom Lil briefly befriends. She is like Angelica Pickles.
Myron Romeo Victor Agustine Leonid Komarovski, Sebastion Marcellino and Alfred Bonaventure (voiced by Leslie Carrara, Margit Furseth and Lauren Tom): "The Blecies" from the episode, Bad Aptitude, who Tommy briefly befriends.
Miyume Kiyoko (voiced by Shuko Akune): A member of the Japanese club whom Kimi befriends in the episode, Memoirs of a Finster.
Kiyoko Lee (voiced by Janice Kawaye): A member of the Japanese club whom Kimi befriends in the episode, Memoirs of a Finster.
Yoshi Hinata (voiced by Scott Maruyama): A member of the Japanese club whom Kimi befriends in the episode, Memoirs of a Finster.
Julia Lauren Mizuno Alcroft (voiced by Janice Kawaye): A classmate in one of Chuckie and Kimi's classes in "Memoirs of a Finster".
Amelia Carnes (voiced by Candi Milo): She ran against Chuckie and Izzy in the safety commissioner race of the Season 2 episode, "Izzy or Isn't He".
Edith Johnson (voiced by Danielle Harris): A nerdy girl who seems to like Chuckie.
Mac DeVanny (voiced by Amy Gunzenhauser): A one-off character from the two-part special Interview With a Campfire.
Buster Carmichael (voiced by Bumper Robinson): Buster is Susie's eldest brother and he appeared in "In the Family's Way".
Edwin Carmichael (voiced by Ogie Banks): Edwin is another of Susie's big brothers who also appeared in "In the Family's Way".
Yvonne Bobir (voiced by the actress from Kids Incorporated, Nicole Brown): Alisa and Ty's daughter.
Kiki Watanabe: Kimi's new born half-sister. She is the daughter of Wanda and Hiro Watanabe
Darryl Spears (voiced by Dempsey Pappion): Darryl is Angelica's love interest in "Lost at Sea" and "Ladies's Man".
Jean Sears (voiced by Jennifer Hale): Jean is Joe and Luca's son and one of the contortionists at the Cirque Extravaganza Day Camp in the episode, "O Bro, Where Art Thou?".
Pilar Willis (voiced by Tara Strong): Pilar is Joe and Luca's daughter and one of the contortionists at the Cirque Extravaganza Day Camp in the episode, "O Bro, Where Art Thou?".
Stuart "Stu" Pickles, Jr. (voiced by Jack Riley): Stu is Tommy and Dil's father. He is a dedicated inventor. He is also married to Didi. He has or had a hair-trigger temper. He has started to bald, or keeps his hair shorter.
Didi Kropotkin-Pickles (voiced by Melanie Chartoff): Didi is Tommy and Dil's mother. She is currently studying Child Psychology; Didi fears failing somehow as a parent. Her hair is beginning to turn gray as she has a big patch of gray in the middle of her hair. She is also married to Stu.
Stuart "Stu"/"Lou" Pickles, Sr. (voiced by Joe Alaskey, replacing David Doyle, who died during production of Rugrats): Tommy, Dil and Angelica's grandfather and Stu and Drew's father. He is married to Lulu. He appears older than in the before series with hearing disorder, because you notice the hospitalized ear buds lodged in both ears. In the series, it is heard that grandpa is in his early 90's. In one episode it is revealed he was a soldier in the United States Army in World War II. He had a hair-trigger temper.
Lulu Jinkins-Pickles: She is Lou's wife. Also Tommy, Dil, and Angelica's step-grandmother and Stu and Drew's stepmother. Never seen on-screen but often mentioned, she appears in the second feature movie Rugrats in Paris: The Movie. It would seem that Lulu has taken to traveling the world, since she is never mentioned in past-tense (which is implying not being around anymore).
Andrew "Drew" Pickles (voiced by Michael Bell): He is married to Charlotte, is Angelica's father and Stu's older brother and Tommy and Dil's uncle. He is now retired and spends most of his time on the golf course. He also is going bald.
Charlotte Jones-Pickles (voiced by Tress MacNeille): Angelica's workaholic mother and Tommy and Dil's aunt until the fourth season, when she is laid-off. She became a depressed housewife, until she marketed Dil's infamous board game 'Impatience'. She is married to Drew. In the first episode, Charlotte is revealed to have gotten plastic surgery leaving her with a permanent smile, which some viewers found as rather creepy.
Betty DeLeon-DeVille (voiced by Kath Soucie): Phil and Lil's mother. A quintessential jock and avid women's-libber, she is married to Howard. Helps operate the Java Lava Coffee House with Chas and Kira Finster.
Howard DeVille (voiced by Philip Proctor): Phil and Lil's mild-mannered father. He is often overpowered by and kowtowing towards his wife, Betty. He is seen less frequently than the other adults.
Chaz Finster (voiced by Michael Bell): Chas is Chuckie's father and Kimi's step-father and is married to Kira. He owns the Java Lava Coffee House.
Kira Finster (voiced by Julia Kato): Kimi's mother and Chuckie's step-mother. She is married to Chaz and often operates the Java Lava Coffee House with him. She debuted in Rugrats in Paris: The Movie, along with her daughter Kimi. She is seen less frequently than the other adults.
Melinda Calone-Finster: She is Chuckie's birth-mother who died a few months after Chuckie was born. Never seen, only referenced in The Finster Who Stole Christmas and once more in the episode Super Hero Worship.
Lucy Yamico Carmichael (voiced by Hattie Winston): She is Susie and Alisa's mother and Randy's wife. She is also a Harvard-educated Doctor.
Randy Carmichael (voiced by: Ron Glass): He is married to Lucy Carmichael. He is also Susie and Alisa's father. He works as a writer for the famous children's TV series, The Dummi Bears Show.
Alisa Carmichael-Bobir (voiced by Bettina Bush): Alisa is Susie's older sister and she appears only twice on the show. Now 26 years old, she's married to Ty Bobir, and mother to little Yvonne. She had money saved for a house, but gave it to Suzie to pay for an audition chance; however, Suzie was being scammed.
Tyrone "Ty" Bobir (voised by Bumper Bush): Alisa's husband and Yvonne's father.
Boris and Minka Kropotkin (voiced by Michael Bell and Melanie Chartoff), Didi's Jewish parents. They are Eastern European immigants who are always complaining that it wasn't this way in the "Old Country". In Boris's first appearance, it was mentioned Minka was visiting her sister. Minka would soon make appearances though.
Beverly Velma Allcroft-O'Keats (voiced by Ann Magnuson): She is Angelica's teacher at Tommy and Angelica's school. She often gets very emotional. She is in a relationship with the school's Vice-Principal.
Vice-Principal Estes Pangborn (voiced by Clancy Brown): A former wrestling champion with a rough, no-nonsense approach to his job. Most of the students fear him, but Dil considers him a friend, and Mr. Pangborn often asks Dil for advice and help. He is in a relationship with Miss O'Keats. Anytime Pangborn tries a fashion, all the kids at school stop using it; this is seen when Tommy markets Dil's weird ideas to raise money for concert tickets.
Mr. Beaker (voiced by Fred Stoller): He is another teacher at the kids' school. He mostly teaches science, but has been known to teach other subjects. He tells bad jokes, and often speaks in a dead-pan voice. During the episode when Tommy sleepwalk-steals due to the stress of an upcoming test, Beaker claims the test does things to those who tate it, showing a picture of himself before it; he was in much better shape then.
Pepe (voiced by Bronson Pinchot): Pepe is the eccentric school chef. He also coaches the school language team.
Mrs. Smith is one of Angelica's teachers. She goes easy on Angelica gradewise because all Angelica has to do is complain and she will give her a better grade. In the episode "What's Love Got To Do With It" she takes time off because she is pregnant and is going into labor with her baby and Mr. Fisk is her substitute teacher.
Mr. Fisk (voiced by Jason Ritter) is a substitute teacher (that Angelica developed a crush on) for Mrs. Smith (Angelica's teacher who was having a baby) that appears once on the episode "What's Love Got To Do With It" and a cameo in "Golden Boy" He is tall, skinny, and has blonde hair. Most of the girls at the school thought he was handsome. He doesn't put up with Angelica's "laziness" and let her off as easy as Mrs. Smith did and he encourages her to do well. He is the leader of the debate team while he is temporarily a substitute teacher at that school. He then is offered a full-time teaching job in St. Louis, Mo and moves there at the end of the episode. He goes to the big debate one last time to wish Angelica luck and gives her a hug.
Mr. Marsh: Angelica and Susie's math teacher.
Joe Melton (voiced by Wally Wingert): Z's father. Chuckie mistakes him for a burglar in the episode Bad Kimi. He is actually a plumber who, along with Z, does voluntary charity work.
Jonathan Patalas (Voiced by Dan Castellaneta): After years of servitude, he is finally promoted above Charlotte Pickles, resulting in her being laid-off.
Hiro Watanabe (voised by Robert Ito): Hiro is Kimi's biological father. He appeared in "Trading Places" and surprised Kimi with her newborn half-sister. Because he didn't send Kimi a gift for Children's Day, Kimi assumed he now preferred his new daughter, Sambrine, over her; however, Kira and Chaz were actually arranging for him to come visit Kimi instead, with Sambrine and his new wife, Wanda.
Wanda Yoshida-Watanabe: Wanda is Hiro's new wife and the mother of Sambrine Watanabe.
Dr. Lipschitz: A famous child psychologist. Didi and Chas commonly refer to his books for help in raising their children. Unlike Rugrats, he is never seen in All Grown Up!, only mentioned.
Velma "Emica" Blake: Although never voiced in the series, she was voiced by Olivia Hack/Adrianne Frantz in the Rugrats episode, All Growed Up. Her style was inspired from that of the singer T-Boz, who performed a song for Rugrats in Paris: The Movie. Her image was inspired by Gwen Stefani who also sported blue hair in pigtails and jewel makeup at one time.
Martin Costomiris (voiced by Michael Bell): He is a film director and Tommy's all time idol.
Reptar: Tommy's favorite fictional dinosaur and plush toy dinosaur.
The Dummi Bears: A favorite show of the Angelica when she was a baby and toddler. To this day, it's still a favorite show for Kimi. This cartoon still has an occasional mention during the series. The show is written by Randy Carmichael, Susie's father.