During the events of the game, Mario had come down with Bean Fever, Luigi had to go to Little Fungitown, the home of Psycho Kamek to gain Crabbie Grass as a cure for the Bean Fever. In the area, he found Psycho Kamek, a hypnotist. He lacked courage to go find Mario by himself, so he went to Psycho Kamek to hypnotize him into thinking he is Mario. When Psycho Kamek calmed down, he saw that Luigi looked a lot like his brother and accidentally thought Luigi was Mario's number one fan and then Luigi had been hypnotized.
He can be referred to as psychotic, hence the name as he tried to hypnotize a Toad into believing he was himself. Occasionally, Psycho Kamek attempts to hypnotize himself in front of his mirror, making the residents of Little Fungitown call him Psycho Kamek.
- Psycho Kamek is the only character from Mario & Luigi: Superstar Saga to not return in the remake. Instead, he is replaced by Dr. Toadley.
- Psycho Kamek's outfit resembles White Mage's outfit.