ObjectiveTo validate the traditional use of Cissampelos pareira as an antidiabetic agent in streptozotocin–nicotinamide induced diabetic male mice. MethodsAntidiabetic effect of aqueous extract of C. pareira leaves (CPAE) was evaluated at 250 mg/kg and 500 mg/kg body weight, p.o. doses in male albino mice over the period of 14 days. Random blood glucose level and body weight were observed periodically. Liver glycogen level, organ coefficient and other biochemical parameters were also determined after completion of the study. ResultSignificant (p < 0.001) changes were observed in random blood glucose levels of mice after 14 days of treatment period at 500 mg/kg CPAE treatment. Aspartate transaminase, alanine transaminase, alkaline phosphatase, total bilirubin, triglycerides and creatinine levels were significantly (p < 0.05) decreased while liver tissue glycogen and serum protein levels were significantly (p < 0.05) increased after CPAE administration. No significant changes were observed in body weight and organ coefficient. ConclusionsThe present study concluded that the aqueous extract of C. pareira at 500 mg/kg body weight was capable in reducing diabetic attritions so it might be a valuable candidate for diabetes treatment.