The key difference to Resident Evil is that Galerians does not employ gun-based combat, but instead features the use of psychic powers, which make it difficult to fight more than one enemy at a time.

When the AP meter is full, Rion loses control of his powers, releasing a continuous psychic assault that will kill non-boss enemies (except for the first boss) in a single blow.

Using psychokinetic abilities to escape his room, Rion fights hospital security and staff desperately and brutally with his newly discovered psychic powers.

He finds that human experiments related to unlocking psychic potential are being conducted in the hospital as part of a grander, more mysterious plan known as the "G Project".

Rion's father, Dr. Albert Steiner, was a computer scientist who, with his partner Dr. Pascalle, designed a self-replicating artificial intelligence called Dorothy that grew too rapidly for them to control.

Rion must find Lilia to keep the Galerians from supplanting the human race, but in order to do so, he will have to face Dorothy's deranged creations directly.

Jeff Lundrigan of NextGen said in an early review, "An interesting variation on a theme, Galerians puts a slightly different spin on the 'survival horror' genre, offering consistently high production values, a thought-provoking story, and solid gameplay.

Plus, the smooth controls and great audio – including sound effects, music, and voice-acting – complete the game's dark world.

It contained preliminary sketches, character turnarounds, box art, some storyboards, and general artwork from both the games and the OVA, all illustrated by Shou Tajima.