The natural enemy of the arrow-poison frog is the snake called Leimadophisepinephelus, whose toxin resists the poison arrow frog.

Snakes are highly immune to the venom of arrow-poison frogs, but are not completely unafraid of the poison. If the poisonous arrow-poison frog's toxicity reaches a high level, the snake is afraid to speak. So the arrow-poison frogs that Leimadophishisepinephelus kills are less toxic arrow-poison frogs or young frogs that have not yet grown up.

Arrow-poison frogs are among the most venomous creatures in the United States, most of which are found in the rainforests of South America, the most common being the ghost arrow-poison frog, the cobalt-blue arrow-poison frog, and the golden arrow-poison frog. The Golden Arrow Poison Frog is said to be the most poisonous of the Arrow Poison Frogs, being 20 times more toxic than the common Arrow Poison Frog. The Golden Arrow Poison Frog has a toxicity of 2 milligrams, but a dose of just 0.2 milligrams is enough to poison an adult, and 2 milligrams can poison 20,000 rats.