Introduction: Herbal medicine has been a cornerstone of healthcare for centuries, with an estimated 80% of the world’s population relying on it. In Africa, herbal medicine is the backbone of rural healthcare, serving 80% to 90% of the population. Despite its widespread use, the safety of herbal medicine raises a significant concern considering the lack of regulation and testing, particularly in Africa. Microbial contamination is a primary safety risk threatening consumer health. In this systematic review, we aimed to synthesise evidence on microbial contamination in herbal medicines across Africa, provide a clear understanding of the problem, and inform effective public health interventions regarding microbial contamination of herbal medicines in Africa. Method: The systematic review was conducted in accordance with the PRISMA guidelines. A literature search was conducted across PubMed, Web of Science, Science Direct, Scopus, and Google Scholar using appropriate search terms. Eligible studies were selected based on predetermined criteria, and data were extracted and analysed. Results: The review included fifty eligible studies in Africa, with a combined sample size of 1996, of which 1791 showed microbial contamination. Bacterial contaminants were reported in 98% of studies, with Escherichia coli (62%) being the most reported bacteria, followed by Staphylococcus aureus (57%), and Bacillus spp. (55%). Fungal contaminants were reported in 70% of studies, with Aspergillus spp. (40%) being the most reported, followed by Penicillium spp. (27%) and Candida spp. (26%). Parasitic contaminants were reported in 2% of the studies reviewed. A total of 70 bacterial species, 37 fungal species, and 6 parasite species were identified in this review. Conclusion: Herbal medicines in Africa pose significant health threats to consumers due to the high prevalence of diverse microbial contaminants and clinically significant pathogens. This emphasises the need for stricter regulations and quality control measures in the production, sale and use of herbal medicines.