Diabetes mellitus is the most common endocrine disorder that impairs glucose homeostasis resulting in severe diabetic complications including retinopathy, angiopathy, nephropathy, and neuropathy causing neurological disorders due to perturbation in utilization of glucose. Hypoglycemic activity was detected in aqueous extract ofPassiflora ligularis, a traditionally used medicinal plant, using streptozotocin (STZ, 30 mg/kg body weight) induced diabetic rat model. Oral administration of aqueous extract ofPassiflora ligularisto diabetic rats for 30 days resulted in a decrease in blood glucose. The diabetic rats had decreased levels of serum total protein, albumin, globulin, and albumin/globulin ratio as compared to control rats. In addition, the activities of hepatic and renal markers were significantly elevated in diabetic rats as compared to control rats. Treatment with aqueous fruit extract ofP. ligularisand glibenclamide reversed these parameters to near normal. Extract at a dose of 400 mg/kg given orally for 30 days showed significant elevation in enzymatic (SOD, catalase, and Gpx) and nonenzymatic antioxidants (vitamin C, vitamin E, and reduced glutathione). Plant extract treated groups showed significant decrease in lipid peroxidation (LPO). Aqueous extract ofPassiflora ligularisfruit can decrease the blood glucose and reduce the oxidative stress by removing free radicals in diabetes.