The Section of Amphibians and Reptiles maintains a collection of over 207,500 specimens and ranks as about the ninth largest amphibian and reptile collection in the US. Ninety percent of them are fluid preserved; others are preserved as skeletons, skins, mounts, or cleared and stained preparations.

The collection includes the largest and most complete collection of Pennsylvania amphibians and reptiles in existence, and significant collections from adjacent states, particularly Virginia, West Virginia, and Maryland. There are collections from all parts of the United States, and most parts of the world including major collections from the Caribbean, Mexico and Guatemala, Belize, Paraguay, northern South America, Spain, South Africa, Cameroon, and India, and Sri Lanka. The collection of North American freshwater turtles is among the largest in the world.

Notable historic collections rich in type specimens are the Taylor Philippine collection, the Le Boutellier collection of South American snakes, and collections from early Museum expeditions to the Isle of Pines and Angola. Collection data are completely computerized. The collection is without a Curator at present, but Collection growth has averaged 1–2% per year. There are approximately 35 new research loans a year handled by the Collection Manager, and around 80 research data inquiries are filled annually.

Research is supported by a library with an outstanding collection of 19th-century herpetological literature (Gunther Collection) and over 22,000 reprints.