Mario vs. Donkey Kong: Minis March Again! is an action/puzzle game similar to the previous game in the series. However, rather than using gesture-based controls to guide the Mini-Mario toys, they are now activated by tapping them or being bumped by other toys. Once the Minis start, they cannot stop (much like in Lemmings, and it's up to you to guide them to the exit and protect them from enemies and obstacles. Before the level starts, you can examine the layout and prepare game pieces so that you can guide the Minis to safety.
Even though you cannot control the Minis directly, you can move blocks around by tapping them with the stylus, allowing you to create steps, bridges and walls. Certain objects, such as conveyor belts, springs and walls can also be adjusted to block or guide the Minis. If a Mini bumps into an enemy, spikes or falls too far, they will break. In addition to this, once the first Mini goes through the exit door, the other Minis must reach it within a certain time or the door will close without them. The final level before the boss features a Locked Door - one of the Minis has a key, and you must guide them to the door first to unlock it and allow the other Minis to enter. After completing all the main levels in each world, you must face off against Donkey Kong. Your goal is to use the Mini Marios as ammo to shoot him and take down his health to beat him and progress to the next stage.
The game also features a level editor. As you progress through the levels, you can use new level templates based on the worlds you have completed.