Several species of reptiles possess morphological adaptations necessary to survive the varying and sometimes harsh conditions of barrier island life. Many of these animals, for instance, have tough skins that exclude salt and retain moisture. Still others exhibit behavioral adaptations that limit their exposure to severe temperature or salinity.

The box turtle (Terrapene carolina), one of the island's terrestrial reptiles, has the ability to retreat completely within its shell and will burrow under vegetation to escape extreme weather. Assateague also hosts five species of aquatic freshwater turtles and three species of sea turtles, including the official Maryland State reptile, the Northern Diamondback Terrapin (Malaclemys terrapin terrapin). One of the island's more charismatic species, Diamondbacks are unusual in that they are one of the very few species of turtle that prefer estuarine habitats. They reside in all of the waters surrounding Island, but are most common in the salt marshes that border the bay. These turtles are a common sight to visitors paddling through these areas during the warmer months.

Though not common, lizards can occasionally be seen on Assateague. Both five-lined skinks (Eumeces fasciatus) and northern fence lizards (Sceloporus undulatus hyacinthinus) live in forested and shrub thicket areas on the island. They feed on small terrestrial invertebrates and will sun themselves on rocks, tree stumps, and other exposed areas within reach of a close hiding place.

Of the 19 species of snake living on the neighboring mainland of the Delmarva Peninsula, only six are found on Assateague, and all are non-venomous. Some wide-ranging species like the black rat snake (Elaphe obsoleta obsoleta) can be found in most of the island's habitats. The eastern hognose snake (Heterodon platirhinos) - which is often mistaken for the copperhead - prefers beaches, dunes, and grassy areas, while the northern water snake (Nerodia sipedon sipedon) prefers salt marshes and freshwater or brackish ponds.

Several factors are thought to account for the discrepancy in the species present on the island and those of the mainland. Geographic isolation and the difficulty posed for most reptiles in crossing the salt waters of the bay are some obvious causes.  It is suspected that humans have also played a role by intentionally introducing some species to the island. Harsh conditions, as well as limited range size and habitat types, may also restrict the species that can successfully survive on Assateague.