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Medarot 4 was released in 2001 for the Game Boy Color. Like its predecessors, it was released in two versions: Kabuto Version and Kuwagata Version.

The game follows Ikki Tenryou and his friends in the town of Omikuji. A new teacher by the name of Ryuuko Yamikumo gets hired at Ikki's school and confiscates all of the class' Medarotches and deletes everyone's data, forcing them to start over in order to train them. Meanwhile, there are rumors of a group called the "Four Kings" wreaking havoc in Omikuji. Medarot 4 incorporates many of the gameplay changes made in Medarot 3.