The stem of Bryophyllum pinnatum (Crassulaceae), used in ethnomedicine for the treatment of various diseases, was screened for secondary metabolites and antimicrobial activity on Salmonella typhi, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus subtilis, Candida albicans and Aspergillus niger. Phytochemical analysis showed the presence of alkaloids, glycosides, proteins, carbohydrates, saponins, steroids, tannins and terpenoids in both the methanol and aqueous extracts. The antimicrobial activity result showed that the methanol extract significantly (P < 0.01) demonstrated antibacterial action against B. subtilis and S. aureus at 100, 50 and 25 mg/ml concentrations, using the agar diffusion technique. The aqueous extract also significantly (P < 0.01) showed antibacterial action against S. typhi and B. subtilis at the same concentrations. Both extracts did not demonstrate any antimicrobial activity against P. aeruginosa, C. albicans and A. niger. S. aureus showed the lowest minimum inhibitory concentration (MIC) of 6.29 mg/ml in the methanol extract, while S. typhi showed the highest MIC of 9.98 mg/ml in the aqueous extract (significant at P < 0.01). The results validate the use of B. pinnatum stem in ethnomedicine.