DeGuglielmo was born in Cambridge, Massachusetts, and was raised in Lexington, Massachusetts. One of three children (an older brother Charlie, and younger a Sister Cristina), he is first generation Italian-American, as his father (Carmine Giuseppe DeGuglielmo / legally changed his name to Charles Joseph DeGuglielmo) emigrated to the US in 1954 with his family as a teenager, from a village outside of Avellino, Italy. His mother (June Dorothy Galassi) was born in Boston, and of Italian and French Canadian heritage. 
DeGuglielmo played both offensive and defensive tackle at Lexington High School (MA) under legendary Massachusetts high school football coach, Bill Tighe. During that time, Lexington High School won two Middlesex League Championships and played for the Division I Super Bowl title against nationally ranked Brockton High School (MA). Moving on to play collegiately at Boston University, he red-shirted his first year (1986) at BU. Despite being a non-scholarship "walk-on," he ultimately became a four-year letterman at Boston University from 1987 to 1990. DeGuglielmo trained under world renowned Strength and Conditioning guru, Mike Boyle, who was at the time the Terriers' head strength and conditioning coach. Playing for three different head coaches in five years, and three different offensive line coaches in his first three seasons, he persevered and was voted captain of the 1990 Terriers. The second of his head coaches was Chris Palmer, future head coach of the Cleveland Browns. Palmer and DeGuglielmo would reunite in 2007 at the NY Giants. His final offensive line coach was Tony Sparano, who went on to become the head football coach of the Miami Dolphins. Sparano would later hire Deguglielmo as his offensive line coach in Miami.  Playing both guard and center, DeGuglielmo was a first-team All-New England selection as well as a two-time Academic All-Yankee Conference selection.
After his playing career ended, DeGuglielmo started off his coaching career at Boston College as a graduate assistant for the 1991-1992 seasons. During this time he served on the staff of then head football coach, Tom Coughlin, and studied under legendary offensive line coach, Mike Maser. Upon the conclusion of this apprenticeship, he left to coach the offensive line at his alma mater, Boston University, from 1993-1996. Leaving four years later he took a similar job at the University of Connecticut, working for head football coach, Skip Holtz. He left Connecticut after the 1998 season for the University of South Carolina, where he coached in a variety of roles including offensive line coach, and tackles and tight ends coach. After five years under Hall of Fame Coach, Lou Holtz, he accepted a job as George O'Leary's first offensive line coach at the University of Central Florida in the winter of 2004. Leaving within a month, he joined the New York Giants staff under head coach, Tom Coughlin, whom he had served as a graduate assistant at Boston College 13 years earlier. In his tenure, the Giants made the playoffs four consecutive years, won a Super Bowl (XLII),and set a franchise record for rushing yards (2,518) and yards per carry (5.0) in 2008. Afterwards, he held the same job for the Miami Dolphins where in 2011 the Dolphins rushed for 1,987 in what was also Reggie Bush's first 1,000 yard season. DeGuglielmo was named the New York Jets' offensive line coach on January 24, 2012. He was fired on February 5, 2013, and spent the 2013 football season as a football analyst for Clear Channel Radio's Sports Talk First Edition, on 560 AM WVOC in Columbia, SC. On January 22, 2014, it was announced that the New England Patriots had chosen DeGuglielmo as the new offensive line coach to replace Dante Scarnecchia, who retired after 30 years with the Patriots. His work as a Patriot began on February 1, 2014. DeGuglielmo had a preliminary agreement to serve as offensive line coach at University of Maryland six days prior to the Patriots' announcement.
DeGuglielmo is married to the former Kimberly Ann McNeil of Port Charlotte, Florida. He is father to Saige Ashley, born August 31, 2008. He currently resides in Prosperity, South Carolina, at his home on Lake Murray.