Background: There is an urgent need for new antimicrobials, due to the increase in drug resistance. Current studies suggest that, by 2050, in the absence of major improvements in drug discovery, more individuals will die from drug-resistant bacterial infections than from cancer. This will result in a cumulative effect on the global gross domestic product of as much as 100 trillion dollars. To discover new drugs, new targets, and lead compounds are badly needed. Natural products of plant biodiversity are a key source of starting points for novel antimicrobial agents with activity against sensitive and resistant bacterial strains. The current study is timely and of a high impact, since it sought to validate anecdotal efficacy of aqueous extracts from selected medicinal plants conventionally used against microbial infections, namely, leaves from Ocimum suave Willd. (Lamiaceae), roots from Plectranthus barbatus Andrews (Lamiaceae), and roots from Zanthoxylum chalybeum Engl. (Rutaceae). Methods: The study plant parts were collected from Msambweni Sub-county, Kwale County, Kenya. Agar well diffusion method was used to evaluate the antimicrobial activity of the extracts against methicillin-resistant Staphylococcus aureus (MRSA) (ATCC 1385), Escherichia coli (ATCC 25922), S. aureus (ATCC 25923), and Bacillus cereus (ATCC 11778). Results: Root extract of P. barbatus was found to be the most active of the studied extracts exhibiting mean inhibition zone values of 18.67 mm, 20.00 mm, and 25.33 mm in S. aureus, MRSA and B. cereus strains, respectively, after 24 h of incubation. All the studied extracts did not exhibit activity against E. coli. In addition, the aqueous leaf extract from the leaves of O. suave did not display antimicrobial activity against the tested organisms. Conclusion: These findings justify the continued ethno pharmacological utilization of P. barbatus and Z. chalybeum extracts against bacterial infections in traditional herbal medicine by various local communities. Furthermore, the current findings lay a strong foundation for further investigation of extracts from P. barbatus and Z. chalybeum for isolation, identification, and characterization of bioactive molecules responsible for the observed antimicrobial activity. These molecules could serve as templates for the discovery of a new class of antimicrobial agents for the management of economically important bacterial infections.