Sepsis and its development of multiple organ dysfunction pose a serious threat to human life and health. Sepsis is a hot issue that experts in the critical field are committed to solve. It is a heterogeneous, infection-induced systemic inflammatory response syndrome based on endothelial dysfunction, and it is still a huge burden on the global health system. As a well recognized immune cell, the endothelium is the primary site of attack by pathogens, toxins, or endogenous injury signals, which cause activation of endothelial cells and consequently damage to their function or structure. Although the latter may help to eliminate the infection and limit the dissemination of the infection to some extent, the excessive and persistent inflammatory response will also lead to a subsequent storm of cytokine and organ damage, causing irreversible damage to the organism. Glycocalyx is the first barrier on the surface of endothelial cells, it is also the first line of defence for endothelial cells under attack in sepsis, which has a great significance on endothelial function. Many studies have found that a variety of immune inflammatory responses involving the glycocalyx also play a key role in the development of sepsis. This review will give a brief overview of the factors, mechanisms and various treatments targeting glycocalyx injury in sepsis at present.