This study investigates the effect of fatty acid and sterol rich extract from the stem back of S. roxburghii (MESS) on hyperglycemia, hyperlipidemia, and oxidative stress induced by high fat diet/streptozotocin (HFD/STZ) in rats. The results indicate that MESS (100 and 400 mg kg−1) reduces fasting blood glucose (FBG), serum lipids including total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), aspartate aminotransferase (AST), alkaline phosphatase (ALP), alanine aminotransferase (ALT), creatinine, blood urea nitrogen (BUN), and glycated hemoglobin (HbA1c). In addition, MESS significantly elevates antioxidant enzymes activities including superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) and suppressed malondialdehyde (MDA) and myeloperoxidase (MPO) content in the kidney and liver tissues. Furthermore, MESS enhances insulin secretion and ameliorate histological alterations in the pancreas, kidney, and liver treated diabetic rats. These results demonstrate that MESS exerts potent anti-hyperglycemic, antihyperlipidemic, and antioxidant effects and may have potentials to prevent diabetes. Practical Applications: The effects of the stem back of S. roxburghii (MESS) on hyperglycemia, hyperlipidemia, and oxidative stress induced by high fat diet/streptozotocin (HFD/STZ) in rats are investigated. The results show that supplementation with MESS counteracted hyperglycemia, hyperlipidemia, and oxidative stress in diabetic rats indicating its ameliorative effect on diabetes and hyperglycemia induced oxidative stress. This research provides a theoretical basis for the development of functional nutraceuticals from MESS diabetic patients.