||It is of great significance to reduce the imflammation caused by reactive oxygen species (ROS) for sepsis treatment. Herein, biocompatible transition metal dichalcogenide (TMD) nanosheets were exploited as stable and powerful antioxidants for sepsis treatment. To this end, TMD nanosheets were exfoliated and functionalized by an amphiphilic polymer in an aqueous solution. The exfoliated TMD nanosheets showed unique cellular scavenging activities for various types of ROS and nitric oxide (NO) in BMDMs stimulated by lipopolysaccharide. It was found that WS2 nanosheets exhibited the highest activity for reduction of inflammatory factors in the living cells via intracellular ROS scavenging. In addition, WS2 nanosheets showed the excellent performance in sepsis-induced mouse models, leading to an increase in their survival rate.