This study investigates the antihypertensive, antioxidant, and cardioprotective effects of Aloin following Langendorff rat isolated heart technique, the main bioactive compound of Aloe vera L., using both experimental (The myocardial ischemia-reperfusion (IR) model, the determination of endogenous myocardial antioxidant enzyme activities, and histopathological examination of myocardial tissue) and computational approaches. To contextualize its potential, Aloin's activity was compared with Verapamil, a standard cardiovascular drug that, despite its efficacy, is limited by side effects and contraindications, particularly in patients with heart failure or hypersensitivity. In vivo experiments demonstrated that Aloin exerts significant cardioprotective and antihypertensive effects in a dose-dependent manner, in some cases matching or surpassing the efficacy of Verapamil. Aloin improved cardiac performance, as shown by increased left ventricular developed pressure (LVDP) and decreased left ventricular end-diastolic pressure (LVEDP) and coronary perfusion pressure (CPP). It also enhanced antioxidant defenses by elevating superoxide dismutase (SOD) and catalase (CAT) activities, while reducing oxidative stress, evidenced by lower malondialdehyde (MDA) levels. Complementary POM analyses confirmed Aloin's non-toxic profile and identified pharmacophoric features underlying its bioactivity. Collectively, these findings highlight Aloin's strong potential as a natural therapeutic agent for hypertension and cardiovascular protection, warranting further clinical evaluation.