<p>Cardiovascular diseases (CVDs) are a major burden on the global population. This causes structural deterioration and disruption of the myocardium. A multitude of studies has demonstrated that an elevation in intracellular calcium (Ca²⁺)_i through the calcium-sensing receptor (CaSR) is associated with the onset of various CVDs. CaSR is believed to be involved in different processes, including proliferation, differentiation, cell death, gene regulation, and hormonal secretion. Calhex₂₃₁ is a calcilytic drug, which negatively modulates CaSR and attenuates (Ca²⁺)_i influx. Calhex₂₃₁ has shown a therapeutic implication in the realm of cardiac fibrosis, remodeling, hypertrophy, myocardial infarction (MI), cardiomyopathies, pulmonary artery hypertension, myocardial ischemia-reperfusion injury (IR), and heart failure (HF). Numerous studies demonstrated Calhex₂₃₁ has shown cardioprotection through various signaling pathways and reduced damage to organelles within cells. This review aims to establish its potential utility in managing a number of CVDs and associated post-complications.</p>