Purpose: To provide an overview of the ethnomedicinal uses and pharmacological activities of Croton megalobotrys as to understand its potential value and importance in primary health care systems of local communities throughout its distributional range.Methods: The literature search for information on ethnomedicinal uses and pharmacological activities of C. megalobotrys was undertaken using databases such as Web of Science, BMC, Science Direct, Elsevier, Scopus, PubMed and Scielo. Other relevant literature sources included books, book chapters, websites, theses, conference papers and other scientific publications.Results: Croton megalobotrys is an important herbal medicine in southern Africa used as an abortifacient and purgative,and as remedy for human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) opportunistic infections, malaria, muscle aches or pain, sexually transmitted infections (STIs) and skin infections. The chemical constituent of C. megalobotrys is mainly composed of alkaloids and cinnamate derivative isolated from the stem bark. The biological activities demonstrated include antibacterial, antiplasmodial, anti-HIV and radical scavenging activities.Conclusion: The historical traditional usage of C. megalobotrys as herbal medicine in southern Africa calls for detailed phytochemical and pharmacological properties of the species aimed at identifying the compounds responsible for its wide usage as an herbal medicine.Keywords: Alkaloids, Croton megalobotrys, Ethnopharmacology, Primary health, Southern Africa