Geckos have many natural predators, the main one being snakes. Large spiders, birds and other mammals also eat geckos.

When faced with a potential predator, many geckos can lose their tail. This self-amputation or autonomy assists the gecko in escaping because the detached tail wriggles and distracts the predator, allowing the gecko to escape. In most cases, the gecko will grow a replacement tail made of cartilage. After the danger subsides, a gecko will often return to its detached tail and if it is available, the gecko will eat it. Geckos can also escape predators by using its toe pads that are designed to climb vertical surfaces smoothly.