Different extracts and fractions of five selected indigenous South African medicinal plants, namely, Cissampelos capensis, Geranium incanum and three Gethyllis species, were subjected to phytochemical screening and testing for cytotoxicity using the brine shrimp lethality bioassay, and antimicrobial activity assays against nine microbes, which included three fungal species, three Gram negative and three Gram positive bacteria.The majority of the extracts tested positive for the presence of tannins, phenolics and flavonoids, while in selected cases, phytochemical tests suggested the presence of essential oils, glycosides or alkaloids. The methanol extract of Gethyllis gregoriana displayed the highest cytotoxicity levels. Generally, the highest levels of biological activity were shown to reside in the methanolic extracts, while hexane extracts revealed very low to zero activity. The total tertiary alkaloid (TTA) of C. capensis was mostly active against Bacillus subtilis, a Gram +ve bacteria. The trends observed for the cytotoxicity assay were in agreement with those observed for the antimicrobial assay.