<p>Antihypertensive medications exhibit heterogeneous effects on zinc homeostasis, with potential clinical implications for patients at risk of zinc deficiency (ZnD). This review summarizes the effects of antihypertensive medications on zinc homeostasis, including urinary zinc (UZn) excretion, serum (SZn) and red blood cells (RBCs) zinc concentrations and the potential risk of ZnD. Angiotensin converting enzymes inhibitors (ACEIs), particularly captopril (CPT), reduce SZn by 5–13% and increase urinary zinc excretion 1.4- to 3.8-fold, with combinations with diuretics amplifying renal zinc loss up to 10.6-fold. Diuretics alone increase UZn loss by 1.6- to 3.7-fold, with minor or variable effects on SZn. Calcium channel blockers (CCBs), including verapamil and amlodipine, cause modest reductions in SZn (4.5–25.5%) and elevate RBCs zinc by 6%, whereas β-blockers (BBSs, i.e., atenolol, metoprolol) and angiotensin receptor blockers (ARBs, losartan, valsartan) resulted in decreased SZn (3.5–11%) and different effects on RBCs zinc (− 3.3% to + 3.8%). Overall, ACEIs and diuretics have the most significant impact on zinc metabolism, primarily through enhanced renal excretion, while other medications had mild effects. The important clinical take-home message of this review is that long-term use of ACEIs and diuretics may increase the risk of ZnD, particularly in older adults, patients with diabetes (who already exhibit increased UZn losses and impaired zinc metabolism), or those with low dietary zinc intake. Clinicians are therefore advised to consider zinc status and provide supplementation when deficiency is suspected.</p>