The petroleum ether, chloroform, methanol, and water extracts of the leaves, stem bark, and root of Diospyros mespiliformis were studied for their antimicrobial activities. The crude extracts showed broad spectrum antimicrobial activities against 9 Gram-positive bacteria, 8 Gram-negative bacteria, and 6 fungal strains. Of the four extracting solvents, chloroform produced extracts with the best antimicrobial activities, while the chloroform extract of the root exhibited the highest antimicrobial activity. Some tetracycline resistant strains of Staphylococcus aureus and gentamicin resistant strains of Pseudomonas aeruginosa were sensitive to some of the extracts tested. Preliminary phytochemical screening revealed the presence of the following metabolites: anthraquinones, tannins, triterpene, saponins, steroids, and sugars and the absence of alkaloids. The antimicrobial activities observed are discussed in relation to the chemical constituents reportedly isolated from several species of this plant and their traditional uses.