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In order to evaluate the ethnomedical uses of plants as remedy for malaria, in Southwestern Nigeria, six crude methanol extracts obtained from five plant species, identified and selected from ethnomedicine, were studied for in vitro anti-plasmodial activity and cytotoxicity. The antiplasmodial properties were evaluated in vitro, using the lactate dehydrogenase assay against Plasmodium falciparum (multi drug resistant K1) and the cytotoxicity activities were assessed using KB nasopharyngeal cell line. Thereafter, three of the crude extracts were fractionated and subjected to activity studies. Methanol extracts of three of the plant extracts; Cassia siamea stem bark, Tithonia diversifolia leaf and Cajanus cajan leaf, were found to display intrinsic anti-plasmodial properties with IC50 values of 24.9 µg/ml, 52.9 µg/ml and 53.5 µg/ml, respectively. Fractionation of three crude extracts using organic solvents led to acquisition of twelve fractions, of which the ethyl acetate fraction of C. cajan displayed the highest activity with IC50 value of 15.6 µg/ml. The other active fractions were the aqueous methanol of C. siamea bark and ethyl acetate fractions of Gossypium arboreum, both displaying anti-plasmodial activities, with an IC50 value of 31.3 µg/ml. The crude methanol extract of T. diversifolia was found to be most toxic in the cytotoxicity assay, with an ED50 value of 3.6 µg/ml and least selective to the malaria parasites. The ethnomedicine of southwestern Nigeria could provide leads for the discovery of antimalarial drugs.