Young twigs and leaves of Caesalpinia bonduc (Linn) Roxb is used in the Southwestern part of Nigeria, as an antimalarial medicinal decoction together with other medicinal plant. In order to discover new antimalaria drug or drug lead and also to verify the traditional use of C. bonduc in this area, the in vitro antiplasmodial activity of crude extract, solvent fractions and compounds isolated from C. bonduc were investigated. In vitro antiplasmodial evaluation was carried out using chloroquine sensitive strain of Plasmodium falciparum FCR-3 and selective toxicity determination was investigated using sensitivity study on Mouse mammary tumor FM3A cells as a host model. Ethyl acetate and petroleum ether soluble solvent fractions of C. bonduc showed antiplasmodial activity with EC50 values of 16 and 18 μg/mL and selectivity index (SI) of 0.69 and 0.29 respectively. Bioassay guided fractionation of C. bonduc led to the isolation of seven flavonoids, 7-hydroxy-4'-methoxy-3,11- dehydrohomoisoflavanone (1), 4,4'-dihydroxy-2'-methoxy-chalcone (2), 7,3'-dihydroxy-3,11- dehydrohomoisoflavanone (3), Luteolin (4), quercetin-3-methyl ether (5), Kaempferol-3-O-b-D-xylopyranoside (6) and Kaempferol-3-O-a-L-rhamnopyranosyl-(1®2)-B-D-xylopyranoside (7). Structures of compounds 1 to 7 were elucidated by spectroscopic methods. Compound 2 exhibited moderate antiplasmodial activity with EC50 and SI values of 33 μM and 0.33 respectively while compounds 1, 3 to 7 showed insignificant antiplasmodial activity. The investigation revealed that the moderate antiplasmodial activity exhibited by the solvent fractions of C. bonduc might be mediated by 4,4'-dihydroxy-2'-methoxy-chalcone.