Prior to the events of Kid Icarus, Medusa co-ruled Angel Land with Palutena as the Goddess of Darkness. Whereas Palutena fostered the growth of humanity, Medusa hated their kind and took to drying up crops and petrifying people. Palutena, in a fit of anger, changed Medusa into a cyclopic, snake-haired monster and banished her to the Underworld. Despite this, or perhaps because of it, Medusa vowed one day to overthrow Palutena and retake her position in the Palace in the Sky.
Medusa is voiced by Cree Summer in the English version ofKid Icarus: Uprising.