The game is quite similar to the Professor Layton series of games available on the Nintendo DS. The player directs Wolf around the screen by clicking where they want to investigate or who they want to talk with. Puzzles are uncovered by examining the scenery and talking with the different characters. The game contains 60 puzzles; if the player gets stuck on any of them it's possible to unlock 3 different hints per puzzle, each costing a hint key.
New hint keys can be earned by completing one of the six brain training exercises. These were designed in close collaboration with the neuroscientists of Brain Center International whom are responsible for the famous NeuroActive Program. These exercises are each designed to help with specific functions of the brain.
Big Brain Wolf follows the story of an asthmatic, vegetarian wolf who happens to be a genie in training. As the story progresses, it becomes apparent that the protagonist's mother has eaten someone. It's up to the player to prove her innocence. Along the way, players will meet various fairy tale characters; including Tom Thumb, Pinocchio, and Gepetto.