Plant derived antimicrobial co mpounds that have no or minimal to xicity to host cells are considered candidates for developing new antimicrobial drugs. Safety is therefore critical in the formulation of antimicrobials. The aim of this study was to investigate the cytotoxic effects of some South African med icinal plant extracts. The methanolic and aqueous extracts of nine South African medicinal plants were screened for cytotoxic activ ities against MAGI CC5+ cells using MTT assay.The nine plant extracts used in the MTT assayrevealed Herb 2 (Cyanthula inculata) as the most potent extract identified with activity of (1.4 Cc 50 values of 25.6 mg/ ml) and induced over 50% of cell deaths, followed by herb 3 (Croton grattismus) and Herb 4 (Cassine trasvaalensis) with activ ity of (0.2 Cc 50 values of3.7 mg/ ml) each. The herbs that induced the least cell death, were herbs 5 (Capris tomentosa) and 7 (Hypoxis hemerocallidea), with the activity of (0.05 Cc 50 values of 0.9 mg/ ml) each. Of the nine p lant extracts, Croton grattisimus and Lycium inerme 2(22%), exh ibited minimal to xicity on MAGI cells and 7(77.8%) exh ibited 50% to xicity. In a similar study 2(22%) of the methanolic ext racts exhib ited anti-HIV1 IIIB activit ies and against Mycobacterium tuberculosis (TB) only one med icinal plant extract (Lysium inerme) exhib ited 29% act ivity. In this study, a systematic evaluation of cytotoxic activit ies of methanolic extracts made fro m tested med icinal plants showed minimal to xicity on cell lines. Therefore, such plants could serve as sources for natural antimicrobial therapeutic agents.