American Alligators (Alligator mississippiensis) are known to consume venomous Pit Viper snakes, apparently with no ill effects. Alligators handle venomous and nonvenomous snakes similarly during consumption, indicating that alligators may possess a physiological resistance to venom. In our study, we tested the ability of alligator blood sera to inhibit the activity of two of the primary toxins in Eastern Copperhead (Agkistrodon contortrix) venom, hemolytic toxins and snake venom metalloproteinases (SVMP). Specifically, we compared relative venom activity following incubation with alligator sera to a venom-only control as well as venom incubated with serum from a species lacking venom resistance (House Mouse; Mus musculus). In comparison to controls, alligator sera significantly reduced SVMP activity, although we observed no effect of alligator sera on hemolytic activity. Interestingly, we detected individual variation with respect to hemolytic activity such that inhibition was positively related with both alligator length and body condition. Our results provide evidence that alligator serum is capable of inhibiting at least one of the primary toxins present in pit viper venom.