Magnesium (Mg) plays a critical role in various biological processes, and chronic kidney disease (CKD) can disrupt Mg homeostasis, leading to hypomagnesemia, which is associated with increased vascular calcification. Vascular calcification is a significant risk factor for cardiovascular morbidity and mortality in CKD patients. Both in vitro and animal studies suggest that Mg may protect against vascular calcification by inhibiting hydroxyapatite and calciprotein particle formation, limiting osteogenic differentiation of vascular smooth muscle cells (VSMCs), and modulating signaling pathways such as Wnt/β-catenin. Clinical trials investigating Mg supplementation in CKD patients have yielded conflicting results, leading to a state of equipoise. This review summarizes current knowledge on Mg handling in health and CKD, the mechanisms by which Mg may prevent vascular calcification, and the evidence from clinical studies on Mg's efficacy. It also discusses future research directions, emphasizing the need for further investigation into Mg's role in vascular calcification and its potential as a therapeutic target. The review highlights the importance of understanding Mg's mechanisms of action and the need for well-designed clinical trials to determine its effectiveness in preventing vascular calcification in CKD patients.Magnesium (Mg) plays a critical role in various biological processes, and chronic kidney disease (CKD) can disrupt Mg homeostasis, leading to hypomagnesemia, which is associated with increased vascular calcification. Vascular calcification is a significant risk factor for cardiovascular morbidity and mortality in CKD patients. Both in vitro and animal studies suggest that Mg may protect against vascular calcification by inhibiting hydroxyapatite and calciprotein particle formation, limiting osteogenic differentiation of vascular smooth muscle cells (VSMCs), and modulating signaling pathways such as Wnt/β-catenin. Clinical trials investigating Mg supplementation in CKD patients have yielded conflicting results, leading to a state of equipoise. This review summarizes current knowledge on Mg handling in health and CKD, the mechanisms by which Mg may prevent vascular calcification, and the evidence from clinical studies on Mg's efficacy. It also discusses future research directions, emphasizing the need for further investigation into Mg's role in vascular calcification and its potential as a therapeutic target. The review highlights the importance of understanding Mg's mechanisms of action and the need for well-designed clinical trials to determine its effectiveness in preventing vascular calcification in CKD patients.