Background: Increased cardiovascular mortality due to multifactorial progressive arterial stiffness in chronic kidney disease is influenced by the disturbed balance between inducers and inhibitors of vascular calcification. The potential to enhance the protective effects of vascular calcification inhibitors through effective therapy could stimulate further research and collaboration. This systematic review aims to give a grounded overview of vascular calcification inhibitors and their serum levels in different stages of chronic kidney disease to demonstrate the dynamics during stages of declining kidney function and renal replacement therapy. Methods: The systematic review was registered in the PROSPERO database on August 30th, 2023 (CRD42023459169). and conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA). Results: We screened 463 articles, of which 192 were eligible, and investigated vascular calcification inhibitors or included values of their serum levels. Serum levels of fetuin-A, vitamin D, FGF-23, Klotho, osteopontin, matrix GLA protein, osteoprotegerin, magnesium, and sclerostin are demonstrated in tables and sparingly studied substances with a perspective towards better treatment options are found in Supplementary Table. Conclusion: Endogenous vascular calcification inhibitors could serve the role of valuable biomarkers to detect the process earlier and estimate the effect of treatment. The serum levels presented demonstrate the dynamics in different stages in chronic kidney disease and propose practical feedback for personalized treatment strategies. Manifold possible vascular calcification inhibitors under research set a promising starting point for more effective therapeutic interventions.