Most infectious diseases affecting humans are zoonotic in origin, with mammals serving as the main reservoirs. Frequent interactions between humans and animals, especially in the context of their use for food, medicine, and other purposes, pose significant public health risks, as recently demonstrated by the SARS-CoV-2 pandemic. In traditional medicine, many species—some of which are also used as food—are valued for their therapeutic versatility, that is, the diversity of medicinal uses attributed to each species. This study investigates the role of zoonotic potential in the selection of mammals used in traditional medicine at a global scale. We compiled data on 411 wild mammal species across 17 orders, identifying 5.146 associated pathogens, of which 2.778 (53.9%) also infect humans. Most diseases transmitted by these species are caused by viruses (33.4%), bacteria (23.3%), and helminths (22.3%). These mammals are used to treat at least 500 diseases or symptoms, and 4.3% of the species show high therapeutic versatility (RI > 1). Our results indicate that species selection is shaped by both biological and cultural factors, with zoonotic potential being the most influential: species with a higher risk of disease transmission tend to be less used. These findings highlight the importance of incorporating zoonotic risk into research and policies regarding the medicinal use of wildlife.