Background Over five billion people globally rely on a plant- and animal-based pharmacopoeia for their healthcare needs. The inhalation, topical application, subcutaneous injection, or ingestion of animal products - such as faeces, fur, milk, blood, brain tissue, or meat - likely facilitates the spill over of zoonotic pathogens. Certain practices use species known to be involved in the transmission of pathogens of public health relevance, such as reservoir species for filoviruses, poxviruses, and coronaviruses. These practices and the public health risk they entail have not been previously reviewed and analysed for the African continent. Methods We first conducted a systematic review of literature using web-scraping algorithms targeted at peer-reviewed (PubMed) and peer-reviewed or grey literature (Google Scholar) databases, followed by manual search of reference lists published before July 30th, 2023. We used terms encompassing zoo*, animal*, health*, practice*, tradition* followed by a list of all 54 African countries in combination with Boolean operators. We then created a categorical score reflecting the risk of zoonotic pathogen spill over for each recorded zootherapeutic practice, and compared this risk between geographic regions and between demographic groups. Findings A total of 53 studies were included, reporting the use of over 2,000 zootherapeutic practices. Half of the included studies were published after 2020. Nigerian, Ethiopian, Tanzanian and South African practices were comparatively well documented. The mean total risk score was significantly lower in western (p < 0.0001), central (p < 0.003), and southern (p < 0.0001) Africa, compared to eastern Africa, while there was no significant difference between eastern and northern Africa. Further, we found that physically sick children are overall at increased risk for pathogen spill over (p = 0.001) compared to physically sick adults, and that pregnant or lactating women are exposed to animal tissues of significantly greater infectious potential (p = 0.032). Interpretation The WHO recently hosted its first global summit on Traditional, Complementary and Integrative Medicine (TCIM), highlighting its importance to fulfil SDG 3: Health and Wellbeing. Where other forms of healthcare are unavailable or inefficient, zootherapeutic practices can provide valuable solutions to acute, chronic, physical, and psychological issues. However, significant risks of zoonotic disease transmission exist. This article aims to guide research on sustainable alternatives to mainstream medical treatments that balance cultural significance and public health.