Introduction: Phytolacca dodecandra L’Hér. is a native plant of sub-Saharan Africa and Madagascar which is traditionally used for various ailments. Concerned with the scope of the available evidence, we designed a scoping review to critically analyze scientific evidence on P dodecandra’s pharmacology, toxicity, and phytochemistry to validate its ethnomedical use. Methods: We searched without language restriction in MEDLINE, Google Scholar, Scopus, Embase, and Web of Science through December 2019. Both published and unpublished articles were assessed for relevance and reviewed. Results: Of 600 articles retrieved through database search, a total of 48 articles were finally included. The butanol extract of berries was more potent molluscicidal than aqueous extract. The berries had also miracidial, anthelmintic, antifungal activity, and antibacterial effect against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Salmonella spp. The methanol extracts of roots had an antifungal effect against Candida albicans, Cryptococcus neoformans, Microsporum gypseum, and Trichophyton mentagrophytes. Phytolacca dodecandra was toxic to aquatic invertebrate and fish. The fishes were up to 4 times more sensitive than snails. Saponins were the main phytoconstituent isolated from berries. Terpenoid and phenolic were abundant in leaves and bark extracts. Conclusions: Studies validated the traditional use of P dodecandra against snails, worms, and various bacterial and fungal infections. Limited phytochemical data call for future research to focus on isolation of compounds; test their toxicity and activity; and establish mechanism of action.