BackgroundMalaria is a leading cause of death in Nigeria. AimAntimalarial activity of Stemonocoleus micranthus stem bark was evaluated in mice with an objective to finding scientific evidence for its use as antimalarial remedy in South-east Nigeria. MethodsAntiplasmodial activities of hydro-methanolic extract and solvent fractions (hexane, chloroform, ethyl acetate and aqueous) of S. micranthus stem bark against chloroquine-sensitive Plasmodium berghei infected mice were determined using suppressive and curative procedures. Chloroquine was used as positive control. In vitro models, DPPH (1, 1-diphenyl-2- picrylhydrazyl) radical scavenging, FRAP (ferric reducing antioxidant power) and TPC (total phenolic content) were used to assay antioxidant activity of the test samples. Phytoconstituents of the active fractions were analysed by GC-MS. ResultsChemosuppressive effect exerted by extract (50, 100, 200, 400 mg kg−1) and fractions (20, 40, 80 mg kg−1) ranged between 54.14 – 67.73% and 59.41–94.51% respectively. Curative effects was also dose dependent. In both models, ethyl acetate was the active fraction. At low doses the animals lived longer but not protected (D0 – D29). At high doses, extract (400 mg kg−1), active fractions (80 mg kg−1) and chloroquine (5 mg kg−1) the animals were fully protected.The extract and fractions exhibited antioxidant potentials which could have contributed individually or synergistically to antimalarial activities reported in this study. Oral LD50 was estimated to be greater than 4000 mg kg−1, in mice. ConclusionThe results of this study may have provided support on traditional therapeutic use of the plant in treatment of malaria.