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Teleglitch is a top-down action game based on the roguelike principle. The player guides a character through a randomized environment with permadeath. The game is set in the future on in a military research facility on the planet Medusa-1C, 30 light years from Earth. The player's character is a scientist who researches necrotic tissue reactivation. Something goes wrong and when the scientist wakes up discovers he is the only survivor as all other personnel has been killed and the others have been micro-chipped and mutated and are controlled by the facility's AI.

The game features retro-pixelated graphics with a camera that zooms based on the size of the current room. When walking through a corridor or first entering a room, visibility is initially limited to the line of sight. There is a strong emphasis on a careful approach and resources are limited. The environments are procedurally generated for each session and a checkpoint is only available after completing a certain set of levels. The character can be moved around and can aim in any direction. There are melee weapons, ranged weapons and explosives. Scavenging is important to gather new weapons, ammo and items. These can also all be crafted into more powerful versions or entirely new items can be constructed through crafting. The environment also contains terminals with dossiers that explain more about the monsters and the events.