Ethyl acetate extract of the Stem bark of Piliostigma reticulatum was tested against clinical bacterial strains including; Escherichia coli, Klebsiella aerogenes, Proteus vulgaris, Pseudomonas aeruginosa, Salmonella typhi, Streptococcus pyogenes, Staphylococcus aureus, Serratia marscences, Shigella dysenterie and Yersinia enterocolitica using the agar well diffusion method of Perez, (1990). Purified extract were subjected to spectra analysis using NMR and GCMS.Result obtained revealed that the plant extract has antibacterial properties against E. coli, Str. Pyogenes, K. aerogenes, S.aureus, and Sh. dysenteriae with zones of inhibition ranging from 10mm – 20mm at 100mg/ml of extracts. Lower zones were observed for lower concentrations. Essential oils discovered in purified extract include sesquiterpenes, esters, fatty acids, alcohols and palmitic acids. However, sesquiterpenes were found to be most abundant. Piliostigma reticulatum justifies its use in traditional medicine and some of the mode of action include destroying the microorganism’ ability to produce catalase and the ability to stimulate non-opsonic phagocytosis.