Abstract: This study aimed to evaluate the effectiveness of the extraction method employed in traditional herbal medicine by comparing the antimicrobial and anti-inflammatory activities of the leaf extracts of Piliostigma reticulatum and Piliostigma thonningii. The suitability of the two species as substitute was also determined. The agar dilution method was employed to compare the activity of crude leaf extracts of the two species against sixty bacterial and fungal isolates selected from diverse genera. The antimicrobial spectra of the extracts from both species were very similar. In 44 (73.3%) of the test strains, MIC values for the two extracts were identical and in 6 (10.0%) the MIC values differed by only one dilution factor. Chlorocresol was used as standard. The crude extract and solvent fractions obtained from the leaf of P. reticulatum were evaluated for anti-inflammatory activity using the carrageenan-induced rat paw oedema model. The aqueous fraction at 100 mg kg-1 produced the highest inhibition of oedema (61.2%), while the crude extract at 100 mg kg-1 exerted a low anti-inflammatory effect (13.2%). Indomethacin at 5 mg kg-1 inhibited oedema by 86.2%. This study has established that P. reticulatum and P. thonningii have similar antimicrobial spectra and anti-inflammatory activity. The traditional extraction method is not effective in extracting the antimicrobial agents from the plants.