Background:Entada africana (EA) is a medicinal plant used in West Africa for the treatment of malaria fever, but its efficacy against malaria is yet to be scientifically validated. Our study explores the antimalarial potential of the ethanol leaf extract of EA.Methods: The antiplasmodial activity of EA against chloroquine-sensitive (HB3) and chloroquine-resistant (FcM29) Plasmodium falciparum was determined as well as its peripheral antinociceptive and anti-inflammatory properties. The effect of the extract on human monocytic (THP-1) cells was recorded as a measure of cytotoxicity, whereas the inhibitory effect on heme detoxification was evaluated as a possible mechanism of antiplasmodial activity.Results: At a concentration of 100 μg/mL, EA was noncytotoxic and displayed moderate antiplasmodial activity against HB3 and FcM29 (IC50=26.36 and 28.86 μg/mL, respectively). It also exhibited concentration-dependent inhibition of synthetic heme (IC50=16 mg/mL). The extract (200 mg/kg body weight) showed significant (pConclusions: These findings suggest that peripheral antinociceptive effects and parasiticidal activity of EA contribute to its antimalarial properties and it can be further explored as effective therapy against malaria infection.