The present study aims to evaluate the antibacterial profile of Brysocarpus coccineus and Zanthoxylum piperitum in Nigeria. The antibacterial efficacy of methanolic leaf extracts of Brysocarpus coccineus and Zanthoxylum piperitum was determined against six clinical isolates and three typed cultures respectively. The percentage yield of the extracts was calculated, and it showed 5.6% for Brysocarpus coccineus and 4% for Zanthoxylum piperitum. Preliminary phytochemical screening of the two extracts showed the presence of saponins, steroids, glycosides, flavonoids and resin. The extracts effectively inhibited the growth of Escherichia coli and Bacillus subtilis at different concentrations. The extract of B. coccineus inhibited S. aureus, K. pneumonia and P. aeruginosa at different concentration, while that of Z. piperitum inhibited S. aureus and P. aeruginosa at different concentration. B. coccineus extract had its MIC at 6.25 mg/ml against clinical isolate of Escherichia coli and Bacillus subtilis. Z. piperitum methanolic extract had its MIC at 6.25 mg/ml against clinical isolate Bacillus subtilis. All the plants extract had no activity against Salmonella typhi, and B. coccineus had no activity against Klebsiella pneumonia. The results of statistical analysis (ANOVA) of the B. coccineus showed that F-cal. is greater than F-tab. This means there is a significant difference in the activity of the extract, while that of Z. piperitum showed that F-cal is less than F-tab. meaning there is no significant difference in the activity of the extract. This reveals the importance of leaf extracts of B. coccineus and Z. piperitum in the control of resistant microbial strains.