Ethnopharmacological Relevance. Development of resistance to antimalarial drugs by Plasmodium falciparum is still rampant, and there is an urgent need for novel drugs to either standalone or to partner artemisinin for treatment of malaria. Traditionally, plants have, over the years, been a good source of antimalarial drugs. Efficacy and safety of such plants need to be scientifically authenticated. Aims, Materials, and Method. This study investigated the in vitro antiplasmodial activity, cytotoxicity, and genotoxicity of aqueous extracts of Acanthospermum hispidum DC, Alstonia boone (De Wild), Cocos nucifera L, Cymbopogon citratus (DC.) Stapf, Morinda lucida Benth, Psidium guajava, Phyllanthus niruri L, and Senna siamea Lam. Results. Five out of the eight plants, A. boonei stem bark, S; siamea Lam root, M. lucida Benth leaves, P. niruri, and A. hispidum DC whole plants, showed varying degrees of antiplasmodial activity against the asexual stage of the parasite. The most active extract against chloroquine-sensitive (3D7) and chloroquine-resistant (Dd2) P. falciparum strains is the A. hispidum extract which yielded a mean inhibitory concentration at 50% (IC50) of 3.66 µg/ml and 3.71 µg/ml for 3D7 and Dd2, respectively. This was followed by S. siamea Lam with 3.95 µg/ml for 3D7 and 4.47 µg/ml for Dd2. The IC50 values of the A. boonei extract against 3D7 and Dd2 P. falciparum parasites were 5.13 µg/ml and 3.62 µg/ml, respectively. For the M. lucida Benth extract, the least IC50 value was 6.46 µg/ml. All five extracts exhibited dose-dependent antiplasmodial activity. Assessment of the genotoxic effects the A. hispidum extract by the comet assay revealed substantial damage to P. falciparum DNA. Conclusion. This study demonstrates that the crude extract of A. hispidum DC, one of the plants used traditionally to treat malaria, inhibits the growth of P. falciparum in vitro and could be a potential source of antimalarial drug. The report has highlighted genotoxic and cytotoxic effects of the selected plant extracts on human leukocytes as well.