The object of Mr. Do! is to score as many points as possible by digging tunnels through the ground and collecting cherries. The title character, Mr. Do (a circus clown—except for the original Japanese version of the game, in which he is a snowman), is constantly chased by red monsters resembling small dinosaurs, and the player loses a life if Mr. Do is caught by one. The game is over when the last life is lost.

Cherries are distributed throughout the level in groups of eight. 500 bonus points are awarded if Mr. Do collects eight cherries in a row without stopping. A level is complete when all cherries are removed, all monsters are destroyed, "EXTRA" is spelled, or a diamond is found.

Mr. Do can defeat the monsters by hitting them with his bouncing "power ball" or by dropping large apples on them. While the power ball is bouncing toward a monster, Mr. Do is defenseless. If the ball bounces into an area where there are no monsters to hit (such as behind a fallen apple), Mr. Do cannot use it again until he has retrieved it. When the power ball hits a monster, it then reforms in Mr. Do's hands after a delay that increases with each use.

Mr. Do or the red monsters can push an apple off the edge of a vertical tunnel and crush one or more monsters. If an apple falls more than its own height, it breaks and disappears. Mr. Do can also be crushed by a falling apple causing a loss of life.