Midnight Mutants is an action game with adventure elements. You play the part of Jimmy visiting Grampa on Halloween. Unfortunately, on this Halloween Dr. Evil has returned from the grave and captured Grampa in a pumpkin, and now you have to save him! As Jimmy you'll need to explore Grampa's mansion and the surrounding lands in order to find items which can be used to defeat enemies (including Dr. Evil) as well as safely reach new areas. The lands have become cursed, however, and there will be many obstacles on your quest including killer bats, zombies, werewolves and more.
The gameplay revolves around exploration, puzzle-solving, and combat. Jimmy has two life meters, one for health and one for blood. Some creatures are poisonous on contact and reduce the blood meter, while others reduce the health meter. If either runs out, the game is over. Grampa's spirit will occasionally provide clues or other useful information to aid Jimmy in his quest. The game features an isometric point of view, with some larger areas scrolling horizontally or vertically to follow the action.