Two players control two soldiers, named Ricky and Mary, who fight their way through large eight-way scrolling levels while rescuing their comrades who are being held by aliens. After they have rescued a certain number of hostages, the exit opens and they can pass through it in order to fight the end-of-level guardian. If this monstrosity is defeated, they are then able to move onto the next stage. Alien Syndrome features two player simultaneous gameplay and pickups which assist the player, including better weapons and maps of the current level.