Medusa of Soul Eater is voiced by: Houko Kuwashima (Japanese), Luci Christian (English)
Medusa is the first major antagonist introduced in the story, a snake-themed witch who contains over a thousand snake familiars inside her body that she can use in her Vector Arrow spell. She can also create arrow-shaped panels on the ground called Vector Plates that throw anyone standing on them in the direction they point. Medusa is a scientist who developed Black Blood, a substance that enhances madness within people, and aims to use it as part of her experiment to enable the world to evolve and no longer be stagnated by the DWMA's actions. Medusa is resolute of her goals to the point of experimenting on her own child Crona whose purpose is essential to her overall scheme.
Prior to the start of the story, getting Mabaa's permission under false pretenses, Medusa infiltrated the DWMA under the guise of a school nurse to find Asura's location, amassing an entourage to help her revive the Kishin with Black Blood. Though defeated by Franken Stein shortly after her plan succeeds, Medusa survives the destruction of her original body by hiding her soul inside a snake and later possessing the body of a young girl named Rachel. When her plans are impeded by Arachne, kidnapping Crona to make it seem to be sister's doing, Medusa forms a truce with DWMA to dispose of Arachnophobia and provides leverage with the demon tool Brew. But once she acquired Arachne's soulless body, Medusa continues her experiments on Crona for her master plan to have the child be able to assimilate Asura. This plan ultimately culminates with Medusa showing Crona affection for the first time in her child's life, intentionally provoking the confused Crona into killing her.
In the anime adaptation, Medusa uses the truce between her and DWMA to manipulate Stein instead of defeating Arachnophobia. To do so, she forces Crona to implant a magic snake inside of an unsuspecting Marie Mjolnir to worsen Stein's already increasing madness—an act that is present in the manga's plot, but is instead used to keep him from interfering with Medusa's plans—until he runs away from DWMA and joins her. She battles Maka, Marie, and a repentant Crona until Maka defeats her without harming Rachel's body, though she is shown at the end of the anime to have once again survived in the body of a snake (although there is nothing to confirm her soul was inside the snake this time, and she says after her first transfer that she likely wouldn't survive it again without the madness waves from Asura's awakening).