Introduction: In order to contribute to the development of new strategies to fight against malaria, we evaluated the antiplasmodial activity of extracts, fractions and molecules of Cassia siamea on schizonts of Plasmodium falciparum. Materials and Methods: Cassia siamea sterm bark petroleum ether, DCM, ethanol and water extracts sequentially prepared were subjected to bioguided fractionaton by TLC and HPLC coupled to mass on schizonticidal activity on the chloroquinoresistant strain of P. falciparum (FcM29 from Cameroon). The MTT test on the KB and Vero cells allowed to evaluate the cytotoxicy of the active ingredients. Results and Discussion: Fractions Fc (IC50 = 5 ± 1.0 μg / ml) and Fe (IC50 = 1.5 ± 0.98 μg / ml); and molecules P 2 (1.22 ± 0.56 μg / ml), P18 (0.4 ± 0.07 μg / ml), P27 (0.1 ± 0.02 μg / ml) were significantly the most active. These antiplasmodial active principles are not cytotoxic and belong to the groups of alkaloids and triterpenoids. Conclusion: These results justify the tolerance and use of this plant against malaria in traditional medicine in Congo.