Schistosomiasis remains one of the most debilitating Neglected Tropical Diseases (NTDs), with Praziquantel being the only drug of choice. However, dependence on a single drug is threatened by limited access, high cost, and possible resistance. Hence, it is imperative to search for cheaper and locally available alternatives. This study evaluated the antischistosomal activity of the aqueous leaf extract of Vernonia amygdalina, a common Nigerian shrub used both as soup and cure for stomach ailments. Bulinus globosus snails were challenged with miracidia obtained from S. haematobium eggs. Cercariae from infected snails were used to infect 15 albino rats through a modified tail immersion method. The infected rats were divided into five groups of three rats each. Three groups received100mg, 150mg, and 200mg dosesof the extract, a fourth group was treated with Praziquantel and the last group was left untreated. A sixth group remained uninfected, totaling 18 rats. Treatment with V. amygdalina significantly reduced worm load in a dose-dependent manner, with the 200 mg group showing the greatest reduction. Gross pathology revealed that the untreated rats exhibited liver mottling and hepatomegaly, which were markedly reduced at 200 mg. Clinical observations showed hair regrowth, absence of haematuria, and normal grooming comparable to the praziquantel-treated group. Lower doses produced partial improvements.Overall, the aqueous leaf extract of Vernonia amygdalinademonstrated potent antischistosomal activity, and could serve as a promising alternative therapy.