Garter snakes were long thought to be non-venomous, but discoveries in the early 2000s revealed that they produce a neurotoxic venom. Despite this, garter snakes cannot seriously injure or kill humans with the small amounts of comparatively mild venom they produce and they also lack an effective means of delivering it. In a few cases, some swelling and bruising has been reported. They do have enlarged teeth in the back of their mouth but their gums are significantly larger and the secretions of their Duvernoy's gland are only mildly toxic.

Evidence suggests that garter snake and newt populations share an evolutionary link in their tetrodotoxin resistance levels, implying co-evolution between predator and prey. Garter snakes feeding on toxic newts can also retain those toxins in their liver for weeks, making those snakes poisonous as well as venomous.