Sclerocarya birrea (A. Rich.) Hochst, an African widespread plant is known to be used for type 2 diabetes management in sub-Saharan Africa. This review aims to summarize the findings for the pharmacology of S. birrea antidiabetic effects and its in vivo and in vitro toxicity. To collate data on S. birrea, various scientific search engines like PubMed, Scopus, Scifinder, Google Scholar, Web of Science, Wiley Online, SpringerLink, and ScienceDirect were consulted. The data collected on S. birrea were organized in line with antidiabetic pharmacology and toxicology. The plant has shown consistent hypoglycaemic effects attributed to the increase of insulin secretion, glycogenesis and digestive glucose uptake, along with α-amylase and α-glucosidase inhibition. The plant extracts were also associated with the reduction of lipids blood levels, reno-and cardio-protective effects in diabetes mellitus. The extracts exhibited a good safety profile with LD50 ranging from 600 to 3000 mg/kg of body weight depending on the parts used. Several compounds of the extract have been shown to target different receptors involved in glycaemic homeostasis. S. birrea which has demonstrated consistent antidiabetic effects and a good safety profile could be investigated in humans in the reverse pharmacology pattern.