Abstract: Concurrent therapy of herbs with conventional regimen has been extensively reported for alleviating morbidities such as diabetes and cardiac manifestations. One of unique natural remedy that carry abundant potential for ameliorating wide varieties of ailment is garlic. Present research was designed to explore the role of garlic in obviating myocardial dysfunction in diabetic animals, when combined with ramipril and/or gliclazide. Diabetic Sprague Dawley rats received garlic (250 mg kg-1), ramipril (1 mg kg-1) and gliclazide (10 mg kg-1) orally either alone or in combination in their respective groups. At the end of treatment, heart was excised; mounted on modified Langendorff’s set-up; perfused with Krebs–Henseleit solution and subjected to ischemia reperfusion injury. Significantly increased percentage recovery was recorded in heart rate and developed tension during post-ischemia in all treated animals, when compared to diabetic group. Further, depleted Superoxide Dismutase (SOD) and catalase activities were substantially inclined in treated groups. Furthermore, combination of garlic with ramipril was most effective in reverting the ischemic damage, whereas, garlic with gliclazide prevent beta cell degeneration. Moreover, histopathological observations validated biochemical and hemodynamic findings. To conclude, this preliminary observation in animals reveals the beneficial role of adding garlic to conventional regimen of gliclazide and ramipril. Further, a careful clinical evaluation of above combination would provide us an opportunity to standardize and implement in cardiovascular disease management in diabetic patient.