The distal convoluted tubule (DCT) of the kidney plays an important role in blood pressure regulation by modulating Na⁺reabsorption via the Na⁺-Cl⁻cotransporter (NCC). A diet containing high salt (NaCl) and low K⁺activates NCC, thereby causing Na⁺retention and a rise in blood pressure. Since high blood pressure, hypertension, is associated with changes in serum calcium (Ca²⁺) and magnesium (Mg²⁺) levels, we hypothesized that dietary Na⁺and K⁺intake affects Ca²⁺and Mg²⁺transport in the DCT. Therefore, the present study aimed to investigate the effect of a high-Na⁺/low-K⁺diet on renal Ca²⁺and Mg²⁺handling. Mice were divided in four groups and fed a normal-Na⁺/normal-K⁺, normal-Na⁺/low-K⁺, high-Na⁺/normal-K⁺, or high-Na⁺/low-K⁺diet for 4 days. Serum and urine were collected for electrolyte and hormone analysis. Gene and protein expression of electrolyte transporters were assessed in kidney and intestine by qPCR and immunoblotting. Whereas Mg²⁺homeostasis was not affected, the mice had elevated urinary Ca²⁺and phosphate (P_i) excretion upon high Na⁺intake, as well as significantly lower serum Ca²⁺levels in the high-Na⁺/low-K⁺group. Alterations in the gene and protein expression of players involved in Ca²⁺and P_itransport indicate that reabsorption in the proximal tubular and TAL is affected, while inducing a compensatory response in the DCT. These effects may contribute to the negative health impact of a high-salt diet, including kidney stone formation, chronic kidney disease, and loss of bone mineral density.