Conservation policies have often ignored the potential role of traditional cultural practices and their contribution to conservation goals. Recently, there has been growing recognition of the role of cultural practices and belief systems that have the potential to enhance and provide lessons for sustainable resource use and conservation. On the other hand, some local practices, and harmful cultural beliefs can lead to overexploitation and indiscriminate killing of wildlife negatively impacting species populations. This case study approach explores indigenous uses, practices and belief systems, associated with mammalian predators, and how these factors influence tolerance for carnivore conservation. Semi-structured interviews (n = 40) and focus groups (n = 20) including traditional healers and diviners, hunters, and farmers regarding indigenous uses, practices and belief systems associated with nine small carnivore species (avian, and small mammal predators) that persist in agro-ecosystems of the Vhembe District of South Africa. Participants demonstrated considerable knowledge of the utilisation of carnivores for medicines and other cultural uses, as well as several strategies promoting the protection of certain species through traditional institutions, taboos, and as totemic species. The association of some carnivore species with witchcraft and ecosystem disservices related to negative impacts on human health, and predation on domestic livestock, reduced the tolerance for carnivore conservation. Our analysis reveals the challenges and opportunities for reviving traditional practices for carnivore conservation in agro-ecosystems. We conclude that the philosophy of co-management approaches, which advocate for equitable power-sharing, rights and responsibilities between the state, and local resource users, are important components of carnivore conservation outside of protected areas. This is based on the premise that local communities’ voices are acknowledged, heard and integrated into conservation management plans and policies.