H. sabdariffa polyphenolic extract (HPE) was demonstrated to inhibit high glucose-stimulated cellular changes. In this study, we analyzed the composition of HPE and used a type 2 diabetic rat model to test its protective effect. At least 18 phenolic compounds were found in HPE. Treatment with HPE reduced hyperglycemia and hyperinsulinemia, especially at the dose of 200 mg/kg. HPE decreased serum triacylglycerol, cholesterol, and the ratio of low density lipoprotein/high density lipoprotein (LDL/HDL). Diabetes promoted plasma advanced glycation end product (AGE) formation and lipid peroxidation, while HPE significantly reduced these elevations. Immunohistological observation revealed that HPE inhibited the expression of connective tissue growth factor (CTGF) and receptor of AGE (RAGE), which was increased in type 2 diabetic aortic regions. Furthermore, HPE recovered the weight loss found in type 2 diabetic rats. In conclusion, we demonstrated the anti-insulin resistance properties of HPE and its effect on hypoglycemia, hypolipidemia, and antioxidation. HPE has the potential to be an adjuvant for diabetic therapy.