Plant species used by Venda people of South Africa in the treatment of malaria and associated symptoms were evaluated for their antiplasmodial efficacy as well as cytotoxic properties and some showed significant activity.; In vitro antiplasmodial activity and cytotoxic properties were evaluated on 20 indigenous plant species. Ground plant material was extracted in dichloromethane: 50% methanol (1:1). Antiplasmodial activity was evaluated against the chloroquine-sensitive strain of Plasmodium falciparum (NF54). The cytotoxicity of the plant extracts were assessed against mammalian L-6 rat skeletal myoblast cells and the selectivity index (SI) calculated.; Of the 43 plant extracts evaluated, 10 exhibited pronounced antiplasmodial activity (IC50≤5μg/ml) with good therapeutic indices (SI≥10). Lipophilic plant extracts were relatively more potent than polar extracts. Tabernaemontana elegans Stapf. (Apocynaceae) and Vangueria infausta Burch. subsp. infausta (Rubiaceae) extracts displayed significant antiplasmodial activity (IC50<2μg/ml).; Findings of this study partly support the ethnomedical use of the investigated plant species by Venda people as antimalarial remedies. The study also highlights some of the knowledge gaps that require further phytochemical studies on the specified plant species.