Background This present study investigated the antiplasmodial activity of crude extract, and dichloromethane fraction of Artocarpus altilisstem bark and isolated some chemical constituents present in the dichloromethane fraction of the crude extract. Methods Stem barks of A. altilis wereextracted by maceration with 80% aqueous ethanol at ambient temperature. The dichloromethane fraction was repeatedly fractionated and subsequently purified by chromatographic methods using silica gel 60 (230-400 mesh size) and Sephadex LH-20 columns to afford Compounds 1, 2, and3 which were characterised by analysis of their 1D-NMR, 2D-NMR, and HRESIMS spectra data. Antiplasmodial activity of crude extract, and dichloromethane fraction was evaluated using the 4-day chemosuppresive, prophylactic, and curative assays respectively, while antiplasmodial activity of Compound 3 was tested using the 4-day chemosuppresive assay. To rationalize the possible mechanistic basis of the observed antiplasmodial activity, Compounds 1, 2, and 3, were screened against 54 macromolecular targets relevant to the establishment of the malaria infection.