Amlodipine is an angiotensin II type 1 receptor blocker and partial agonist of peroxisome proliferator-activated receptor gamma. Here, we investigated the protective capacity of Amlodipine against high glucose (HG) elicited oxidative. The activity of lactate dehydrogenase (LDH), NADPH oxidase (NOX), superoxide dismutase (SOD), catalase (CAT) as well as the levels of malondialdehyde (MDA), glutathione (GSH), intracellular reactive oxygen species (ROS), and all other in-vitro & in-vivo antioxidant experimental models. Moreover, the direct antioxidant effect of amlodipine was determined by 2,2-azinobis-(3-ethylbenzothiazoline-6- sulphonic acid) (ABTS) assay and protein expression. Amlodipine exhibited antioxidant activity inthe ABTS assay with the IC50 value of 37.5 µM. Additionally, the cell viability, GSH level, SOD and CAT activity were notably elevated by amlodipine. These findings suggest that amlodipine has protective effects on Management of Hypertension and Diabetes Mellitus.