Babysitting Mama is an entry in the Mama series where the player has to take care of a baby through different mini-games. The game comes optionally with a plush baby doll (also available separately) with a gap in the back where the Wii Remote can be inserted. The Wii Remote is then connected to the Nunchuck so the game recognizes movement of the doll combined with the analog stick and buttons of the Nunchuk for the main controls. It is also possible to play without the doll.

The game progresses through many different mini-games such as taking pictures of the baby, feeding, washing, burping, rocking it to sleep, changing diapers, playing with a seesaw or a mobile, stopping it from crying etc. Each mini-game has a different lay-out and controls, often based on timing correctly with room for a few mistakes. Based on the final result a bronze, silver or gold medal is awarded. If the movement of the plush doll is too violent, the game pauses briefly and displays a warning. There are multiple environment such as inside the house or outside in the park. There are six babies to choose from, unlocked gradually: Daniel, Emma, Koyuki, Lucy, William and Yuto, each with their own baby book with six pages to unlock.

Other types of mini-games include feeding multiple babies at once, a crawling race, pushing a swing, a simplified tug-of-war or collecting bottles. The mini-games can be practiced in a training mode and by completing them in the story mode various unlockables are opened up. The game is split up into several levels (pages) with four to five mini-games each. Some of the mini-games are based around mama when she has to swat flies or climb a tree to retrieve her hat. The game has a versus mode for two players simultaneously, each controlling their own doll. After completing the game it is possible to view an album with pictures of all of the baby's activities.