The player uses one of four chess sets (Dexter's, Dee Dee's, Mandark's, or Major Glory's) featuring Dexter's Laboratory-themed pieces in the traditional game of chess. Piece captures are accompanied by animated scenes depicting the defeat of the captured piece. There is also a puzzle mode, which when completed unlocks the hardest game difficulty.
A versus mode allows two players to swap a single Game Boy Advance back and forth or play against each other on two separate Game Boy Advances with two copies of the game. The game's difficulty is geared towards younger players.