Psilerium is a psychic mineral, like Psitanium, however it is psychically disorienting and can cause hallucinations in people with Psilerium poisoning. A large deposit of Psilerium is known to be in the heart of the Rhombus of Ruin, where many vehicles have crashed there due to pilots and captains being drawn in by the Psilerium. Psilerium is a crucial element in Psychonauts: In the Rhombus of Ruin.

It is revealed that if a psychic's defenses are strong enough, they can fight of its effects to a degree, as shown with Razputin Aquato, and how it made the rescue and escape of Truman Zanotto and his teammates possible.