Tom has captured Jerry's five friends: Duckling, Uncle Peco, Tyke, Tuffy and Muscles and has locked them up in five different locations, and it's up to the player (as Jerry) to rescue them. The game features a total of five levels, and all have the same objective: find a way to get to Jerry's friends. The player moves Jerry around, avoiding enemies and obstacles while collecting musical notes.
The gameplay involves navigating through levels, meeting Angel Jerry and Devil Jerry along the way, who provide hints and tips. Players encounter doors leading to mini games, which require collecting a certain number of musical notes to gain access. These mini games are designed for young players' skill level and offer increasing difficulty as the game progresses.
The Game Boy Color version of Tom and Jerry in Mouse Attacks features 2D graphics and supports multiple languages, including English, French, German, Spanish, Italian, Dutch, and Danish. Note that there is no save function available in this game.