Sepsis-induced multiple organ dysfunction is a complex condition characterized by inflammation, oxidative stress, endothelial dysfunction, mitochondrial damage, cellular energy failure, and dysbiosis. Recent research has focused on liver and cardiac dysfunction, acute lung and kidney injuries as the primary causes of mortality in sepsis patients. Various novel therapeutics, including melatonin, metformin, palmitoylethanolamide (PEA), certain herbal extracts, and gut microbiota modulators, have shown efficacy in different sepsis models. The research focus has shifted from anti-inflammatory and antioxidative agents to exploring the modulation of energy metabolism and gut microbiota in sepsis. These approaches have shown significant impact in preventing multiple organ damage and mortality in animal models but require further clinical investigation. Understanding the molecular mechanisms of sepsis is crucial for developing effective therapeutic strategies.Sepsis-induced multiple organ dysfunction is a complex condition characterized by inflammation, oxidative stress, endothelial dysfunction, mitochondrial damage, cellular energy failure, and dysbiosis. Recent research has focused on liver and cardiac dysfunction, acute lung and kidney injuries as the primary causes of mortality in sepsis patients. Various novel therapeutics, including melatonin, metformin, palmitoylethanolamide (PEA), certain herbal extracts, and gut microbiota modulators, have shown efficacy in different sepsis models. The research focus has shifted from anti-inflammatory and antioxidative agents to exploring the modulation of energy metabolism and gut microbiota in sepsis. These approaches have shown significant impact in preventing multiple organ damage and mortality in animal models but require further clinical investigation. Understanding the molecular mechanisms of sepsis is crucial for developing effective therapeutic strategies.