Aim: The present study was designed to investigate the effect of different extracts of Excoecaria agallocha L. in the treatment of diabetes and its complications. Diabetes was induced by intraperitoneal administration of streptozotocin (65 mg/kg) for the development of diabetic nephropathy and neuropathy. Diabetic nephropathy was evaluated by assessing levels of fasting blood glucose, glycated hemoglobin (Hb A1C), serum insulin level, albuminuria, serum urea, uric acid, creatinine, and blood urea nitrogen along with altered lipid profile (total cholesterol, triglycerides, low-density lipoprotein [LDL], very LDL, and high-density lipoprotein-cholesterol). Materials and Methods: Oral treatment of diabetic rats with extracts of E. agallocha L. improved renal dysfunction indicated by a significant decrease in urinary albumin; serum creatinine, urea, and uric acid. Moreover, a significant increase in body weight along with a significant decrease in fasting blood glucose and Hb A1C in treated groups was observed. Hyperglycemia-induced oxidative stress in diabetic control rats indicated by a significant decrease in superoxide dismutase and reduced glutathione level with a significant increase in malondialdehyde (thiobarbituric acid reactive substances) levels was also ameliorated by treatment with extracts. Results and Discussion: Development of neuropathy was evident from marked hyperalgesia (thermal as well as mechanical) and tactile allodynia along with reduced Motor nervous conduction velocity (MNCV). An elevated level of nitrite, tumor necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β), and interleukin-1β (IL-1β) were also assessed in the sciatic nerve of diabetic neuropathy animals. Treatment with different extracts of E. agallocha L. significantly attenuated elevated thermal and mechanical hyperalgesia. Elevated tactile allodynia assessed using flexible Von Frey filaments was also reversed by extracts. Treatment with both extracts significantly attenuated the parameters of oxidative stress in sciatic nerve of diabetic neuropathy rats. Furthermore, level of nitrite, TNF-α, TGF-β, and IL-1β significantly increased in the sciatic nerve of diabetic neuropathy animals that were ameliorated by treatment with E. agallocha L. extracts. Conclusion: Histopathological changes in kidney, pancreas, liver, and sciatic nerve of diabetic rats were also reversed by the treatment. These findings suggested that treatment with E. agallocha L. ameliorated diabetes and its complications (diabetic nephropathy and diabetic neuropathic pain).