Background: Sepsis is a systemic inflammatory state associated with acute kidney injury (AKI) and high mortality. However, sepsis induced AKI cannot be efficiently prevented or cured using current antimicrobial therapies and supportive measures. We explored the therapeutic effect of newly developed fructose esters on sepsis-induced AKI (S-AKI). Methods: We used the surface plasmon resonance technique and ultrasensitive chemiluminescence analyzer to characterize the lipopolysaccharide (LPS)/endotoxin binding activity and antioxidant capability of fructose esters. We evaluated the degree of fructose ester gastrointestinal digestion using rat intestinal acetone powder. We examined the therapeutic effect of fructose esters on LPS-induced S-AKI by evaluating the blood and renal reactive oxygen species (ROS) amounts, Caspase 1 mediated pyroptosis, inflammation, microcirculation, and renal dysfunction. Results: Our data showed that the fructose esters are not easily hydrolyzed by the rat intestinal acetone powder implicating its high stability in the gastrointestinal tract. 1,6-dilauroyl-D-fructofuranose (FDL) dose-dependently scavenged H2O2 activity displayed a higher binding affinity to LPS than sialic acid and fructose did. LPS significantly enhanced Caspase 1 mediated pyroptosis and increased leukocyte infiltration, blood and renal ROS amount and BUN and creatinine level, whereas FDL significantly depressed these LPS-enhanced parameters. In addition, the increased plasma inflammatory cytokines levels using LPS could be reduced by intravenous fructose ester FDL treatment. Conclusion: Our data suggest that FDL with antioxidant H2O2 activity can neutralize LPS toxicity using a high binding affinity, and attenuate S-AKI by inhibiting Caspase 1 mediated pyroptosis resulting in ameliorating renal oxidative stress and dysfunction.