This study evaluated the antiplasmodial, hepatic and nephritic effects of fractions of Glyphaea brevis methanol leaf extract in P. berghei infected mice. Mice weighing between 15-30 g were infested intraperitoneally with 0.2ml plasmodium infected blood and left for 3 hours before treatment. Infected test groups were treated via oral route of administration with varying doses (200, 300 and 400 mg/kg body weight) of ethylacetate, N-butanol and residual aqueous portion fractions of the Glyphaea brevis methanol extract and Artemisinin (5 mg/kg b.wt) for four days. N-butanol fraction showed the highest antiplasmodial activity (76.64%), followed by residual aqueous portion (73.25%) and ethylacetate (72.99%); Artemisinin has 86.13%. Serum bilirubin (total and conjugated) concentrations of the untreated group (0.82 ± 0.20, 0.51 ± 0.12) were significantly lower (P<0.05) than those in the infected group treated with 300 mg/kg of the residual aqueous portion (1.36 ± 0.20, 0.76 ± 0.05) respectively. Serum albumin levels showed significant (P<0.05) increase in all the groups treated compared to the positive control. Serum total protein, urea and creatinine levels of test groups were not significantly (P>0.05) different from the positive control group. Conclusively, Glyphaea brevis has substantial antiplasmodial activity and could provide a lead for new antimalarial drug development.