Diabetes mellitus (DM), a metabolic disorder, is the causes of oxidative stress leading to complications in micro- and macro-vascular system. The present study investigated sophocarpine for anti-diabetic potential in vivo in mice model. Sophocarpine administration to diabetic mice significantly (p < 0.05) attenuated glucose content in the plasma. The diabetes mediated lowering of GSH, ceruloplasmin and vitamin E was prevented in mice plasma by sophocarpine administration. Sophocarpine significantly (p < 0.05) reversed diabetes mediated suppression of insulin level and total Hb content in the mice plasma. In sophocarpine administrated diabetic mice C-peptide level was elevated and glycosylated hemoglobin content was suppressed significantly (p < 0.05) relative to diabetic group. Administration of sophocarpine significantly (p < 0.05) repressed diabetes mediated increase in TG and TC levels in dose-based manner. Administration of sophocarpine exhibited preventive role against diabetes mediated pathological damage to pancreas in the mice. Sophocarpine administration to diabetic mice repressed PPARgamma recruitment significantly (p < 0.05) in dose-dependent manner. Sophocarpine prevents oxidative stress mediated pancreatic damage through increase in vitamin E, GSH and C-peptide levels, Moreover, the PPARgamma activity was down-regulated, LDL-c content lowered and HDL-c level elevated in diabetic mice by sophocarpine. Therefore, sophocarpine may be developed for treatment of diabetes, however, further in vivo studies need to confirm the same.