Abstract Background The study of human-nature relationship has made possible to understand the life dynamics of the communities and the biodiversity with which they cohabit. Although there has been a rise of ethnobiological studies over the last decade, little is known about human interaction with herpetofauna in South America and Colombia. In this work, we analyzed the knowledge, perception, and interaction of a local community located in the forest reserve of Quininí (RFPCQ) in Cundinamarca (Colombia), concerning to the herpetofauna that inhabits the area. Methods We performed semi-structured surveys containing 30 questions categorized into three groups: academic knowledge (1), use and cultural beliefs (2), and interactions (3) related to the herpetofauna that occurs in the region. The obtained data in question groups 1 and 2 are presented as a qualitative summary. For the question group 3, we assigned the answers to a hostility value according to the possible reaction of each individual interviewed in a hypothetical encounter with the herpetofauna and built tendency charts in order to see the positive or negative reactions due to the birthplace (urban/rural) and gender (male/female). Results The community recognized the presence of amphibians and reptiles that cohabit their space, as well as their potential habitats. Besides, the role of herpetofauna was recognized in the magical/religious traditions for some inhabitants of the region, mainly associated with the fate and cure of chronic diseases. In general, the perception of amphibians and reptiles varied according to the origin and gender of the people, which tend to have a more positive perception of reptiles than compared to amphibians in most cases. Conclusions Although there was a general lack of knowledge on the part of the inhabitants of the RFPCQ about the biological and ecological aspects of herpetofauna, the population recognized the basic information about the habitats of these animals within the reserve area. There is a wide variety of uses of amphibians and reptiles in traditional medicine. Greater efforts should be made in the transmission and dissemination of knowledge about the ecological functions of herpetofauna.