Sepsis is a severe infectious disease that seriously endangers human health and life, and may cause life‑threatening multiple organ dysfunction. Currently, due to lack of effective treatments, this disease is still a pressing global challenge. Sestrin2 is a highly conserved stress protein, and closely associated with the pathogenesis of sepsis. Interventions on Sestrin2 have potential therapeutic value, and thus have become a hotspot of current research. This review summarizes the biological function and mechanism of action of Sestrin2 in sepsis and its protective effect on multiple organ dysfunction caused by sepsis, in order to provide new ideas and thoughts for the treatment of sepsis.