Abstract: Plant extracts are continuously investigated for their extensive inclusion of biologically active constituents that exert therapeutic activities against many diseases. The aim of this study was to assess the antioxidant/anti-schistosomal activities of the essential oil of the fresh leaves of Melaleuca armillaris (M. armillaris) compared to Praziquantel (PZQ) on normal and Schistosoma mansoni-infected mice. The oil was isolated by hydrodistillation and analyzed by gas chromatography/mass spectrometry (GC/MS). The oil was rich in 1,8-cineole (33.93%), terpinen-4-ol (18.79%), limonene (10.37%) and B-pinene (6.59%). M. armillaris oil (150 mg kg-1, orally) was administered from the second week post infection twice per week for six weeks. PZQ (500 mg kg-1, orally) was administered for two successive days 8 weeks post infection and mice sacrificed one week later. Total protein, Malondialdehyde (MDA), Glutathione (GSH), vitamins C and E, the antioxidant enzymes catalase and superoxide dismutase, as well as liver weights and liver/body weight were determined in the liver tissues. Results showed that, both treatments significantly ameliorated the disturbed levels of GSH and MDA in infected mice. Both vitamins were significantly elevated after treatment with the oil while a significant increase in catalase accompanied by a pronounced decrease in SOD were obtained after treatment with PZQ. Both treatments markedly improved liver and body weights in infected mice compared to the infected-untreated ones. In conclusion, natural plant sources may be used as promising alternative agents to chemical drugs for schistosomiasis treatment, since the latter may result in drug-induced resistance arising from repeated use.