Endogenous bioactive small molecules are characterized by low molecular weight, high biological activity, low immunogenicity, and rapid synthesis and metabolism, play a pivotal role in maintaining vascular homeostasis.Vascular calcification (VC) is a abnormal deposition of calcium and phosphorus in the vessel wall. Endogenous bioactive small molecules such as cardiovascular bioactive peptides, adipokines and gaseous molecules participate in the process of VC through various mechanisms. This review summarises the advances in relationship between endogenous bioactive small molecules and the occurrence, development, and related mechanisms of VC.