Objective: To evaluate in vivo antioxidant activity of latex and leaves methanol extract of Euphorbia helioscopia using mice as experimental animals. Methods: The plant was collected, identified, dried under shade, ground to fine powder and extraction was done. Latex was collected in dried bottles by cutting the stem. Oxidative stress was induced in mice with acute toxic dose of paracetamol administered intrperitoneally. Latex and leaves methanol extract (600 and 1 200 mg/kg) orally, once a day, were given to mice for two weeks. Then oxidative stress biomarkers were measured in tissue homogenates and serum. Results: Leaves methanol extract exhibited prominent in vivo antioxidant effect as compared to latex. Results showed significant rise in antioxidant enzymes (catalase, superoxide dismutase and glutathione) levels at 1 200 mg/kg dose of extract. Thus, extract helped to detoxify the free radicles by increasing antioxidant enzymes levels. Malondialdehyde value decreased significantly with extract (1 200 mg/kg) which was indicator of extract's power to inhibit the generation of free radicals. Extract (1 200 mg/kg) exhibited maximum cure against stress induced changes in liver, kidney, lipid profile parameters and complete blood count. Conclusions: Leaves methanol extract of Euphorbia helioscopia raised antioxidant enzymes levels in mice. It showed hepatorenal-curative effect, hypolipidemic effect and hemostasis potential. Thus, it can help the biological systems to fight against stress induced pathological conditions.