Three hundred extracts were prepared from plants traditionally used in South Africa to treat malaria and screened in vitro for activity against Trypanosoma brucei rhodesiense, Trypanosoma cruzi, Leishmania donovani, and Plasmodium falciparum. For the 43 extracts which inhibited the growth of one or more parasites to more than 95 % at 9.7 µg/mL, the IC50 values against all four protozoal parasites and cytotoxic IC50s against rat myoblast L6 cells were determined. Amongst the most notable results are the activities of Agathosma apiculata (IC50 of 0.3 µg/mL) against Plasmodium falciparum, as well as Salvia repens and Maytenus undata against Leishmania donovani with IC50s of 5.4 µg/mL and 5.6 µg/mL, respectively. This screening is the starting point for a HPLC-based activity profiling project in antiprotozoal lead discovery.