Major minerals—also known as macrominerals—including calcium, phosphorus, potassium, sodium, magnesium, sulfur, and chloride are essential for physiological homeostasis and disease prevention. Emerging evidence highlights their protective roles against cardiometabolic diseases, yet their contribution to promoting healthy aging and enhancing longevity is not fully understood. This review provides a comprehensive synthesis of observational and interventional evidence on the associations between dietary intake, blood levels, and supplementation of major minerals and cardiometabolic outcomes. Collectively, the findings show that sodium reduction and potassium supplementation yield the most robust effects in lowering blood pressure, while higher intakes of calcium and magnesium are inversely associated with the risks of hypertension, metabolic syndrome, type 2 diabetes, chronic kidney disease, stroke, and all-cause mortality. Elevated phosphorus intake and serum phosphorus concentrations are consistently linked with adverse outcomes, whereas emerging data suggest that higher serum chloride may be protective. Major minerals exert their cardiometabolic benefits through multiple biological pathways, including regulation of vascular tone, insulin sensitivity, inflammation, oxidative stress, lipid metabolism, and mitochondrial function. These effects are closely intertwined with mechanisms underpinning healthy aging, suggesting that optimal mineral balance may preserve physiological function, reduce disease burden, and extend health span. Ensuring adequate and balanced intake of major minerals is therefore critical for preventing cardiometabolic diseases and promoting healthy aging. Future research should prioritize prospective studies on understudied minerals, refine dose-response relationships, incorporate biomarker-based assessments, and conduct intervention trials targeting clinically relevant outcomes to fully elucidate the role of major minerals in longevity and health promotion.