• Mallotus oppositifolius is an important medicinal herb in Africa. • It possesses valuable and diverse pharmacological activities. • More than 30 phytochemicals have been isolated and identified from this species. • Phloroglucinols and mallotoxin appear to be the most promising bioactive compounds. • Here the first comprehensive review of M. oppositifolius is presented. Mallotus oppositifolius (Geiseler) Müll.Arg. (Euphorbiaceae) is an important and multipurpose medicinal herb found in different African countries. Its various parts possess several pharmacological activities. However, to date, there is no literature review collating the traditional uses, phytochemistry and biological activities of M. oppositifolius. Therefore, the present review aims to provide a current, relevant and comprehensive summary of the botany, ethnomedicinal uses, phytochemistry, and biological activities of M. oppositifolius. To this end, a review of all published literature was conducted using various online scientific databases. Traditionally, M. oppositifolius is used to treat epilepsy, convulsions, haemorrhages, dysentery, stomach pain, waist pain, chest pain, eye infections, anemia, paralysis, ringworms, skin infections, spasms, kidney infection, inflammation, malaria, fever, headaches, " aseram ", swelling, and tumours. Phytochemical analysis revealed that M. oppositifolius contains several phytochemical classes consisting of sterols, alkaloids, saponins, flavonoids, tannins, and glycosides. The in vivo and in vitro studies conducted on isolated compounds or crude extracts reported several biological activities, viz. antimicrobial, anthelmintic, antidiarrheal, antidiabetic, antioxidant, antiperoxidative, antiproliferative, anti-inflammatory, antinociceptive, antidepressant, anxiolytic, anticonvulsant, cardioprotective and KCNQ1 activities. The leaves of M. oppositifolius are the most commonly used part of the plant and thus the most researched in pharmacological studies. This review reveals that M. oppositifolius has several traditional uses, of which some, such as treatment of epilepsy, convulsion, pain, dysentery, diarrhea, inflammation, malaria and infectious diseases have been tested in pharmacological studies. Its vulnerability to destructive harvesting and overexploitation supports the need to identify the therapeutic applications of the bioactive compounds in clinical trials in order to conserve the plant. [ABSTRACT FROM AUTHOR]