Background: Despite numerous eradication strategies, malaria remains a leading global cause of death, largely due to the spread of multidrug-resistant Plasmodium strains, especially Plasmodium falciparum in Africa. This study evaluates the antiplasmodial activity of endophytic fungal extracts isolated from Alstonia boonei. Methods: Forty-one endophytic fungal isolates from the stem bark, roots, and leaves of Alstonia boonei, identified morphologically, were extracted with ethyl acetate. These extracts were tested for antiplasmodial activity against P. falciparum strains: chloroquine-sensitive (3D7) and multidrug-resistant (Dd2). The 3D7 strain was exposed at ring, trophozoite, and schizont stages to the most active extracts for 24 hours. Parasitemia levels were assessed microscopically, and parasite morphology was examined via Giemsa-stained smears. Chemical profiles of potent extracts were analyzed using phytochemical screening and UHPLC-LIT-MS/MS. Results: The fungal extracts exhibited IC₅₀ values ranging from 3.87 to 48.91 µg/mL (3D7) and 4.92 to 25.18 µg/mL (Dd2). After 24 hours of exposure, parasites at all stages showed pyknotic forms, with cytoplasmic degradation in trophozoites and schizonts. Parasitemia analysis indicated activity across all stages, particularly rings and trophozoites. Ten classes of secondary metabolites were identified, with all eight extracts containing alkaloids. Untargeted LC-MS/MS metabolomics revealed diverse chemical profiles: some extracts (E37 and E15) had distinct metabolomes, while others (E4, E10, and E51) showed strong similarities, suggesting shared compositions.  Conclusion and Recommendations: Endophytic fungi found in A. boonei exhibit antiplasmodial activities and deserve to be exploited further as sources of potential antimalarial agents.