The purpose of the present study was to investigate the protective effects of combined therapy of garlic homogenate and hydrochlorothiazide (HCTZ) in animals with hypertension and myocardial damage. Three weeks of high fructose (10% w/v) in fluid to albino rats resulted in hypertension. They were subsequently administered garlic (125, 250 and 500 mg/kg, 3 weeks in separate groups) and HCTZ (10 mg/kg, 6th week) once daily in their respective groups. At the end of 6 weeks, myocardial damage was induced by subcutaneous administration of isoproterenol (175 mg/kg) for 2 consecutive days. The results showed that garlic and HCTZ increase the lactate dehydrogenase, creatinine phosphokinase, superoxide dismutase and catalase activities in heart homogenate when used concurrently or separately. Further, restoration of normal values in fluid/food intake, body weight, systolic blood pressure, cholesterol, triglycerides, glucose and histopathological scores were observed in all treated groups. Furthermore, histological disturbances and hypertension were significantly ameliorated in treated animals. Moreover, moderate dose of garlic was more effective than low dose, while a high dose of garlic was least effective in correcting electrocardiographic changes. Thus it is concluded that garlic in moderate dose (250 mg/kg) with added HCTZ possesses synergistic cardioprotective and antihypertensive properties against fructose- and isoproterenol-induced toxicities.