BackgroundDacryodes edulisis a plant that belongs to the Burseraceae family. It is widely used traditionally alone or in association with other plants in Cameroonian folk medicine to cure wounds, fever, headaches, and malaria. The aim of this work was to investigate the leaves and stem bark ofD. eduliswith an emphasis on the antiplasmodial and cytotoxic effects of extracts, fractions, and isolated compounds.MethodsExtracts, fractions, and some isolated compounds were subjected to antiplasmodial activity screening in vitro against chloroquine-sensitive 3D7 and multidrug resistant Dd2 strains ofPlasmodium falciparumusing a SyBr Green fluorescence-based assay. The cytotoxicity of active extracts, fractions, and compounds was tested against mammalian Raw cell lines using an in vitro resazurin-based viability assay. The structures of the compounds were determined based on their NMR and MS data. The in vivo toxicity using female BALB/c mice was performed on the most active extract according to the protocol of OECD (2002), guideline 423.ResultsThe hydroethanolic extract from the leaves ofD. edulisdisplayed good antiplasmodial activity with IC50values of 3.10 and 3.56 μg/mL respectively on sensitive (3D7) and multiresistant (Dd2) strains ofP. falciparum. Of the sixteen compounds isolated, 3,3′,4-tri-O-methylellagic acid (4) exhibited the highest antiplasmodial activity againstPfDd2 strains with an IC50value of 0.63 μg/mL. All extracts, fractions, and isolated compounds demonstrated no cytotoxicity against Raw cell lines with CC50> 250 μg/mL. In addition, the most active extract on both strains ofP. falciparumwas nontoxic in vivo, with a LD50greater than 2000 and 5000 mg/kg. A phytochemical investigation of the stem bark and leaves ofD. edulisafforded sixteen compounds, including two xanthones (1–2), three ellagic acid derivatives (3–5), one phenolic compound (6), one depside (7), one triglyceride (8), one auranthiamide acetate (9), one gallic acid derivative (10), four triterpenoids (11–14), and two steroids (15–16). Compounds1,2,5,7,8, and9were herein reported for the first time from the Burseraceae family.ConclusionThis work highlights the good in vitro antiplasmodial potency of the hydroethanolic extract of the leaves of this plant and that of two isolated constituents (3,3′,4-tri-O-methylellagic acid and ethylgallate) from the plant. These biological results support the use ofD. edulisin traditional medicine against malaria.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12906-023-03957-2.