Extracts of seventeen Salvia species used in traditional medicine in South Africa were subjected to biological testing. The potential ability to inhibit the in vitro growth/proliferation of Plasmodium falciparum (FCR-3 strain) and the cytotoxic effects on three human cancer cells [breast adenocarcinoma (MCF-7), colon adenocarcinoma (HT-29) and glioblastoma (SF-268)] and a human kidney epithelial cell line were investigated. The extracts displayed antimalarial activity with IC50 values ranging from 3.91 to 26.01 μg/ml and S. radula displaying the most favorable activity. Two compounds were subsequently isolated from the active fraction of S. radula and identified as betulafolientriol oxide and salvigenin. The two compounds displayed similar or lower antimalarial activity (IC50 values: 4.95 and 24.60 μg/ml, respectively) compared to the crude solvent extract. The concentration required to inhibit 50% of cancer cells ranged between 9.69 μg/ml and 43.65 μg/ml, and between 8.72 μg/ml and 59.12 μg/ml against the MCF-7 and SF-268 cell lines, respectively. The IC50 values determined for the HT-29 cell line ranged from 17.05 to 57.00 μg/ml, with S. lanceolata being the most active. The samples also displayed some degree of toxicity when tested against the human kidney epithelial cells, with IC50 values ranging from 12.12 to 53.34 μg/ml. The in vitro antimalarial and anticancer activities support the historic and present use of Salvia species in traditional medicine.