Objectives For centuries, the genus Entandrophragma (Meliaceae), endemic to Africa, has been used in traditional medicine for the treatment of several illnesses. This review deals with large range of phytochemicals from the genus Entandrophragma and their pharmacological potentials covering the period from 1967 to 2018. Key findings Phytochemical investigations of the genus Entandrophragma led to the report of about 166 secondary metabolites which have been thoroughly summarized herein including some of their semisynthetic derivatives obtained from chemical transformations as well as their biological activities in the medicinal and agricultural domains. The limonoids or meliacins and their precursor called protolimonoids (protomeliacins) reported so far represent almost 69.28% of the total secondary metabolites obtained from the genus, and they display the most potent biological activities. Collectively, both classes of metabolites constitute the markers of Entandrophragma. However, squalene‐type triterpenoids and sesquiterpenoids were reported only from the species E. cylindricum and therefore could be its chemotaxonomic markers. Summary The pharmacological investigations of the extracts of some species exhibited interesting results which support the traditional uses of these Entandrophragma plants in folk medicine. Some compounds revealed promising antiplasmodial and anti‐inflammatory activities and deserve therefore further attention for new drug discovery.