Uncontrolled diabetes can cause a number complication including heart disease, stroke, liver and kidney damage. Presently herbal formulations are mostly recommended to control diabetes due to lesser side effects compared to synthetic drug. Calocybe indica is rich in protein, flavonoids, lipid, fiber, carbohydrate and vitamin and incorporates an ample amount of essential amino acid and low fat product. The present study was aimed to evaluate the antihyperglycemic activity of lyophilized and oven-dried extract of Calocybe indica against STZ-induced diabetic complications as hepatotoxicity and nephropathy. The lyophilized extract (LE) and oven-dried extracts (ODE) of Calocybe indica were administered orally in Streptozotocin (STZ)-induced diabetic rats. After the administration of fractions, blood glucose levels were monitored at specific intervals and it was found that they were significant lowered. The effect of extracts on induced hyperlipidemia was evaluated and found significantly lowered the elevated total cholesterol, triglycerides (TGL) and low density lipoprotein (LDL) level while increased the high density lipoprotein (HDL). The increased level of aspartate aminotransferase (AST), serum alanine aminotransferase (ALT), serum alkaline phosphatase (ALP), lactate dehydrogenase (LDH), urea and creatinine in serum of diabetic rats were observed, and significantly decreased on administration of lyophilized and oven-dried extract of Calocybe indica. The results imply that extract could have a protective effect against hepatic and renal damage induced by oxidative stress in the diabetic rats. The lyophilized extract of Calocybe indica produces higher protective effect compared to oven-dried extract.