Infectious diseases, especially those affecting the respiratory tract, represent a critical problem to health. Crude methanol and water extracts of 10 Venda plants reported to be used ethnomedically in the treatment of respiratory conditions were assessed for their antimicrobial activity against standard strains and clinical isolates of Candida albicans, Haemophilis influenzae, Klebsiella pneumoniae, Staphylococcus aureus, Streptococcus pneumoniae, and Mycobacterium smegmatis using the disc diffusion assay. Four of the 10 plants tested possessed antimicrobial activity, but no activity against K. pneumoniae was observed. Minimum inhibitory concentrations, as determined by the broth microdilution assay, showed three plants, Securidaca longepedunculata, Syzygium cordatum, and Tabernaemontana elegans, to possess MICs </= 1 mg/mL. Phytochemical screening, performed by separation on thin layer chromatography using a variety of mobile phases and visualization with spray reagents as well as UV light showed various classes of compounds in the active extracts. Some of these have been associated with antioxidant activity, as confirmed in this study. Moreover, these extracts showed toxicity in vitro to lymphocytes. Although three plant species with significant antimicrobial activity were identified, there is a need for further scientific evaluation regarding identification of the bioactive constituents, as well as their toxicity.