Two prenylated chalcones, morachalcon A and one other unidentified compound (ME2) were isolated from the stembark of Artocarpus champeden and their structure were determined on the basis of spectroscopic analysis. The antimalaria activities were determined against the growth of P.falciparum in vitro in the presence of a wide concentration ranges of the compound and the results indicated that all compounds exhibited antimalarial activity with IC50 of 0,28µg/ml and 0,35µg/ml respectively. Attempt to determine their mechanism of action by morphological and biochemical analysis of the hemoglobin degradation process in the food vacuole using electron microscopies, SDS-PAGE revealed that morachalcon A and ME2 compounds inhibited hemoglobin degradation. Morphological analysis revealed several changes such as: distention of the food vacuoles, extraerythrocytic location of the parasite in the treated groups. The findings indicated that the two compounds of the A. champeden exhibited potent antimalarial activities through inhibition of the hemoglobin degradation. Therefore, the compounds are potentially developed into novel antimalarial drugs.