This study aimed to determine the antimalarial effect of the Strychnos ligustrina (SLW) wood extracts and to analyze its phytochemicals. The SLW powder samples were macerated with 100% ethanol (E100), 75% ethanol (E75), 50% ethanol (E50), 25% ethanol (E25), and aqueous (A100). The extracts were analyzed by LCMS/MS, and its in-vitro antimalarial activity was tested with Plasmodium falciparum. The results showed that the extract yields of E100, E75, E50, E25, and A100 were 4.3, 5.2, 5.3, 4.7, and 3.6%, respectively. The antimalarial activities of the A100, E25, E50, and E75 extracts were classified as active with IC 50 values of 38.6, 42.6, 42.9, and 43.7 μg/mL, respectively. But, the antimalarial activity of the E100 extract was classified as slightly active with IC 50 values of 87.4 μg/mL. The dominant compounds contained in the extracts of A100, E25, E50, E75, and E100 was the alkaloid compound,