Introduction. The glycocalyx is a gel-like layer covering the membrane of many cells, especially cells of epithelial tissue. It consists of membrane-bound proteoglycans, glycosaminoglycan chains, glycoproteins, and adjacent proteins. Glycocalyx is necessary in maintaining the permeability of vessels, modulation of inflammatory responses and interactions between cells. It is also involved in cell adherence, mobility, mechanotransduction, regulation of the cell cycle and cell. Abnormalities in the structure and function of the glycocalyx underlie many diseases and disorders such as dry eyes disease, diabetes and its complications as well as sepsis. Aim. In this review, we present the current view on the role of glycocalyx in human diseases. Material and methods. This review was performed according to latest literature from the following databases: EBSCO, PubMed, Science Direct, and Springer Link. Analysis of the literature. Pathological mechanisms such as disruption of the glycocalyx barrier and decreased hydration of the ocular epithelial surface cause dry eye disease. During hyperglycaemia, glycocalyx dysfunction occurs, which leads to its dysfunction and activation of the prothrombotic system. Moreover, the increase in the concentration of hyaluronidase leads to increase in the plasma hyaluronan levels and promotion of endothelial dysfunction. Additionally, degradation of glycocalyx in sepsis prevails over increased synthesis of its components strongly favors its enhanced enzymatic degradation. Conclusion. A better understanding of glycocalyx impairment in disease could alter therapeutic strategies to improve patient outcomes.