Background: Diabetes mellitus and hypertension are interrelated diseases sharing common etiology and disease mechanisms that predispose to cardiovascular disease. Hypertension is approximately twice frequent in diabetic patients compared by non-diabetics. Aim: This study was designed to compare the potential cardiovascular beneficial effects and pancreatic β-cell function improvement by vildagliptin as DPP-4 inhibitor and canagliflozin as SGLT2 inhibitor on diabetic hypertensive male albino rats. Materials and Methods: thirty-six rats were randomly divided into 4 equal groups: Control group, Diabetic hypertensive, Vildagliptin-treated diabetic hypertensive (20 mg/kg/day by orally) and Canagliflozin-treated diabetic hypertensive groups (40 mg/kg/day orally). T2DM was induced by I.P. injection of nicotinamide (230 mg/kg) 15 min prior to single dose injection of streptozotocin (60 mg/kg, IP). Hypertension was induced by L-NAME (50 mg/kg, PO) for 4 weeks. The assessed parameters were systolic and diastolic blood pressure (SBP and DBP), fasting blood glucose (FBG), serum endothelial nitric oxide synthase (eNOS), proinsulin, insulin, proinsulin/Insulin ratio, relative expression of MafA gene (β-cells specific transcription factor), Pancreatic and duodenal homebox-1 (PDX-1) gene, and histopathology for pancreas. Results: The results of the present study demonstrated that oral administration of vildagliptin orally for 4 weeks for diabetic hypertensive rats produced beneficial cardiovascular effects as evidenced by the significant reduction of SBP and DBP and the significant increase in serum eNOS level. Moreover, vildagliptin improved pancreatic β-cell function evidenced by the significant reduction of the proinsulin/insulin ratio, the significant increase of MafA and PDX-1 gene expression and the improvement of the histopathological picture of the pancreas.On the other hand, the results of the present study showed that oral administration of canagliflozin orally for 4 weeks for diabetic hypertensive rats produced significant reduction of SBP, but there is insignificant change of DBP and serum eNOS level. Also, it was found that oral administration of canagliflozin significantly increased insulin and proinsulin with no significant change of proinsulin/insulin ratio. In addition, canagliflozin improved pancreatic β-cell function evidenced by the significant increase of MafA and PDX-1 gene expression and the improvement of the histopathological picture of the pancreas; however, vildagliptin has better effects on these pancreatic β-cell parameters. Conclusion: Oral vildagliptin has beneficial cardiovascular effects against hypertension and improves the β-cell secretory function. These effects are greater than those of canagliflozin and thus it can be recommended to use vildagliptin rather than canagliflozin in diabetic patients with co-existing hypertension.