The sodium (Na+) gradient across the plasma membrane, generated by the Na+/K+-ATPase, constitutes the fundamental driving force for a diverse array of secondary active transport systems essential to numerous human tissues. This electrochemical gradient facilitates the function of Na+-dependent cotransporters and exchangers, enabling the translocation of nutrients and ions against their respective concentration gradients, thereby ensuring efficient absorption and systemic distribution. These transport processes are critical for the maintenance of mineral homeostasis and overall physiological equilibrium. This section delineates key Na+-dependent transport mechanisms involved in the cellular uptake and systemic regulation of major minerals such as calcium (Ca2+) and magnesium (Mg2+), essential vitamins including vitamin C and biotin, as well as fundamental nutrients like glucose, amino acids, and phosphate. These substrates utilize Na+ gradients to traverse cellular membranes efficiently, facilitating their participation in metabolic pathways, enzymatic functions, and cellular signaling networks. A comprehensive understanding of these Na+-coupled transport pathways is imperative as their dysregulation is implicated in a spectrum of pathophysiological conditions, including mineral imbalances, metabolic disorders, and nutrient deficiencies. Moreover, this review addresses the hormonal and molecular regulatory systems that sustain sodium homeostasis, notably the renin–angiotensin–aldosterone system (RAAS) and natriuretic peptides, which collectively modulate Na+ levels to preserve fluid balance and physiological function. Elucidating the intricate relationship between Na+ gradients and nutrient transport advances our understanding of mineral and vitamin metabolism and informs the development of targeted therapeutic strategies for related diseases.