The aqueous, ethanolic and petroleum ether extracts of Piliostigma thonningii Fabaceae (Leguminasae) – Caesalpinioidae were tested for bioactive and antimicrobial activities against Staphylococcus aureus (Gram-positive), Escherichia coli and Klebsiella pneumoniae (Gram-negative) and Candida albicans (fungus). The ethanolic extracts inhibited the growth of the pathogenic organisms with zones of inhibition ranging from 6.40±0.42 mm to 10.0±0.22 mm while the aqueous and petroleum ether extracts seem to be ineffective. The leaves of Piliostigma thonningii have high concentrations of flavonoids, tannins, steroids, phlobatannins, saponins, terpenoids, cardiac glycosides, and alkaloids. The ability of the ethanolic extract of the leaves to inhibit the growth of the test bacteria and fungus is an indication of its antimicrobial potency which may be employed in the treatment of microbial infections and degenerative diseases.