The Sierra Madre del Sur (SMS) is a biologically diverse biogeographic province found in south-central Mexico. It is therefore an area of interest from a conservation standpoint. Here we examine the diversity and conservation status of the amphibians and reptiles of the SMS and its subprovinces and determine their similarity with neighboring provinces. We compiled a list of the species of amphibians and reptiles occurring in the SMS and its neighboring provinces from the available literature and gathered information on their conservation status. We also compiled the herpetofauna of the three subprovinces of the SMS (Western, Central, and Eastern). The SMS houses 186 species of amphibians, of which 89% are endemic to Mexico and 53% endemic to the SMS. The SMS also contains 331 reptile species, of which 72% are endemic to Mexico and 23% are endemic to the SMS. The amphibian and reptile diversity of the SMS is concentrated in the Eastern subprovince. The significant number of amphibian and reptile species endemic to the SMS highlights its importance for conservation. Comparison with neighboring provinces shows that the SMS shares 33% of its species with the Transvolcanic Belt, 25% with the Pacific Lowlands and Balsas Basin, and 19% with Veracruzan. The SMS shares 52% of its reptile species with the Transvolcanic Belt, 42% with the Pacific Lowlands, 40% with the Balsas Basin, and 33% with the Veracruzan. The results of a cluster analyses suggest that the SMS does not represent a single unit in terms of its herpetofauna, since the three subprovinces do not cluster together. The Western and Central subprovinces cluster with the Balsas Basin and the Pacific Lowlands, whereas the Eastern subprovince clusters separately. We found that 25.7% of the evaluated amphibian and reptile species in the SMS are included in the International Union for Conservation of Nature’s (IUCN) Red List in some category of conservation concern (amphibians: 54.9%; reptiles: 6.8%). The Eastern subprovince hosts the highest proportion of species of conservation concern (93.8%). It is important to increase the number of areas protected by federal and state governments, especially in the Eastern subprovince, and to promote protections driven by local communities. These actions could help protect the herpetofauna of the SMS, especially the Eastern subprovince, which harbors a unique fauna and deserves special consideration from a conservation standpoint.