The artemisinin partial resistance is believed to be spread to artemisinin-based combination therapy partner drugs. As a result, new antiplasmodial compounds are required to treat resistant malaria infections. In the invention of antimalarial substances, claimed medical plants are precious resources. So, the current study was designed to assess the antiplasmodial effects of Maesa lanceolata in mice. In this study, preliminary phytoconstituent and in vivo acute oral toxicity tests were done. Early infection, established infection, and residual infection tests were employed to determine the antimalarial effects of the test drugs. Three doses (200, 400, and 600 mg/kg) of the extracts were provided orally to the test mice. Analysis of variance (one-way) followed by post hoc Tukey’s test was used to analyze the difference between and within groups. Terpenoids, tannins, saponins, flavonoids, and alkaloids were detected in the phytochemical constituent analysis. Both 80% methanolic crude extract and solvent fractions had no toxic result at the 2000 mg/kg dose. All test drug doses suppressed parasite levels in a significant manner at all tests. The activity of chloroform fraction (maximum percentage suppression, 81.28%) overwhelms the crude extract activity. The curative effects of 80% methanolic crude extract, with a maximum of 80.22% parasitemia suppression, were greater than its suppressive and prophylactic effects. The 400 mg/kg dose of chloroform fraction resulted in a maximum survival period (18 days) than other doses of tested materials. The results of this investigation provide support for the activity of M. lanceolata leaf extract against malaria.