Malaria is still a serious cause of mortality and morbidity. Moreover, the emergence of malaria parasite resistance to antimalarial drugs has prompted the search for new, effective, and safe antimalarial agents. For this reason, the study of medicinal plants in discovering new antimalarial drugs is important and remains a crucial step in the fight against malaria. Hence, this study is aimed at investigating the antimalarial activity of Gymnema inodorum leaf extract (GIE) in Plasmodium berghei infected mice. Aqueous crude extract of G. inodorum leaves was prepared in distilled water (DW) and acute toxicity in mice was carried out. The antimalarial activity was assessed in the five groups of ICR mice employing the 4-day suppressive and curative tests. Untreated and positive controls were given DW along with 10 mg/kg of chloroquine, respectively. Any signs of toxicity, behavioral changes, and mortality were not observed in mice given GIE up to 5,000 mg/kg. GIE significantly (
P
< 0.05) suppressed parasitemia by 25.65%, 38.12%, and 58.28% at 10, 50, and 100 mg/kg, respectively, in the 4-day suppressive test. In the curative test, the highest parasitemia inhibition of 66.78% was observed at 100 mg/kg of GIE. Moreover, GIE prevented packed cell volume reduction and body weight loss compared to the untreated control. Additionally, GIE was able to prolong the mean survival time of infected mice significantly. The results obtained in this study confirmed the safety and promise of G. inodorum as an important source of new antimalarial agents and justify its folkloric use for malaria treatment.