Nitric oxide (NO) dysfunction, oxidative stress, and dyslipidemia are main risk factors associated with the pathophysiology of diabetic complications. In this study, 3,4-dihydroxyphenethyl nitrate (HT-ONO<sub>2</sub>) was designed, synthesized and evaluated, which incorporated hydroxytyrosol (HT) and nitrate. HT-ONO<sub>2</sub> significantly exhibited hypoglycemic activity after oral administration to diabetic mice induced by streptozocin (STZ). HT-ONO<sub>2</sub> also potently decreased plasma triglyceride (TG), total cholesterol (TC) in hyperlipidemia mice induced by Triton WR 1339. Meanwhile, HT-ONO<sub>2</sub> displayed NO-releasing and antioxidant activity both in diabetic and hyperlipidemia mice and in vitro. Moreover, HT-ONO<sub>2</sub> shown definite vasodilation and α-glucosidase inhibition activity in vitro. The results suggested that the hybrid hydroxytyrosol-based nitrate with NO supplement, antioxidant, hypoglycemia and hypolipidemia provided a potential multi-target agent to ameliorate the diabetes mellitus and its complications.