Bio Miracle Bokutte Upa's main character is a baby called Upa that uses a rattle to attack his enemies. When injured by the rattle, the enemy inflates and floats away. These inflated enemies can then be used as temporary floating platforms to climb to higher places or they can also be used as weapons if pushed in any direction. If used as a platform, Upa must not stay on top for too long or otherwise it will explode. But if used as a weapon, Upa has to pounce or use his rattle on the inflated enemy to cause it to careen. The enemy will then ricochet off objects and potentially cause damage to both the protagonist and other enemies if it comes in contact with them.

The game uses a health meter to monitor the player's remaining life which can be replenished by obtaining bottles of milk scattered throughout the levels. A heart icon can also be obtained, increasing the maximum health by one unit for the duration of the current world.

Most items, including the milk bottles and hearts, can be collected by striking special blocks which feature Upa's face. Other items include: Apples, which increase the player's score; hourglasses, which temporarily freeze enemies in place; bells, which give Upa temporary invincibility and the ability to run; and scorpion blocks, which kills all enemies on screen when it is pushed off a platform and hits the ground.