Compositions and methods for treating endothelial glycocalyx include glucosamine, hyaluronan and/or fucoidan, and one or more antioxidants, such as superoxide dismutase, catalase, and/or polyphenol. The compositions improve vascular health by exhibiting beneficial synergistic effects on endothelial glycocalyx over the benefits of taking any single component alone or the sum of reported effects of the individual components. Specifically, components of the composition (1) enhance synthesis of new glycocalyx by (a) providing and (b) increasing production of glycocalyx precursors, (2) protecting existing glycocalyx against damage, such as by oxidation degradation, by (a) providing and (b) increasing production of antioxidants, some of which associate with endothelial glycocalyx, and (3) enhance repair of damaged glycocalyx by (a) providing glycocalyx mimetics and (b) increasing the prevalence of glycocalyx scaffold for association and incorporation thereof.