Oxidative stress is a major cause for development and progression of diabetic mediated peripheral and central complications. The aim of this work is to evaluate the role of Grape Seed Proanthocyanidin (GSPE) extract in attenuating diabetic complications. Forty-five adult male Wistar rats were divided into three groups. Control, non-treated diabetic and diabetic rats treated with GSPE. Diabetes was induced by intraperitoneal injection of streptozotocin. After eight weeks; urine, blood and brain, heart, kidneys, liver tissue homogenate parameters were evaluated. The results showed a reduction in both renal and hepatic function in non-treated group as well as an elevated serum inflammatory markers (TNF-α, hs-CRP and IL-6). In addition, there were an elevation in both serum and different tissue homogenate oxidative stress parameters (SOD, GPx, Catalase and MDA). Treatments with GSPE improve the oxidative stress status in different tissue and improve renal and kidney functions. These finding suggested that GSPE is effective as adjuvant therapy for protection from diabetic complications as well as its potent antioxidant and anti-inflammatory activity.