Numerus studies highlighted benefits of natural flavonoids in the management of diabetes. The present study was aimed to investigate the effects of a high flavonoids containing extract of Rheum turkestanicum on diabetic changes in different tissues. Male Wistar rats were divided into normal and streptozotocin-induced diabetic groups received saline or hydroalcoholic extract of R. turkestanicum root (100, 200 and 300mg/kg) through orogastric gavage for 4 weeks. Serum glucose, HbA1c, lipids, creatinine, uric acid, liver enzymes (alkaline phosphatase, aspartate aminotransferase and alanine aminotransferase), and cardiac enzymes (lactate dehydrogenase and creatine phosphokinase) in diabetic control group were significantly higher compared to normal control group (p<0.001). The extract significantly reduced these factors, increased body weight, and improved both glucosurea and proteinuria. Lipid peroxidation was high in the liver of diabetic rats compared to normal rats (p<0.001) and reverted toward control values by R. turkestanicum. Also, the extract significantly protected the liver, kidney, and heart of diabetic rats against histopathological changes. In conclusion, R. turkestanicum inhibited the development of nephropathy, liver injury, and myocardial damage in diabetes by lowering the serum levels of glucose and lipids, and by inhibiting oxidative stress mediated lipid peroxidation.