Maintenance of the integrity of entire endothelium, glycocalyx included, and therefore of tissue aorta’s homeostasis, depends on the expressions of several molecular pathways and their interactions, such as syndecans molecules. Alterations in syndecans, i.e. quantitative or linking to their shedding, contributes to evocate endothelium dysfunction, which causes damage in the vessel wall due to the increased production of growth-stimulating and pro-inflammatory gene products. Inflammatory processes negatively affect the integrity of the endothelial glycocalyx, a dynamic layer of the luminal portion of endothelial cells composed of proteoglycans, glycoproteins, and glycosaminoglycans, i.e. syndecans. In turn, structural alterations of endothelial glycocalyx influence the coagulative state, increasing pro-thrombotic processes. The family of syndecans constitutes the major component of glycocalyx, or better the major source of cell surface heparan sulfate. It encompasses 4 components: syndecan-1, syndecan-2 and syndecan-4 (since syndecan-3 is expressed only in neural tissue), which have a fundamental role in regulating the events of acute and chronic aorta damage subsequently correlated with the formation of aneurysms. Considering such, the aim of our review is to highlight the current knowledge on the roles of syndecans, and based on the most recent literature, to analyze their relationship with the pathological processes of the aortic wall.