This study investigates the effects of curcumin on septic cardiomyopathy (SCM) and explores its potential mechanisms. Curcumin, a polyphenolic compound with antioxidant, anti-inflammatory, and cardiovascular protective properties, was tested in both in vivo and in vitro models of sepsis. The study found that curcumin significantly improved survival rates, cardiac function, and reduced inflammatory responses in sepsis-induced mice. Mechanistically, curcumin activated sirtuin 1 (SIRT1), increased the expression of mitochondrial biogenesis-related genes (Pgc1α, Tfam, and Nrf2), reduced dynamin-related protein 1 (DRP1) translocation to mitochondria, and restored mitochondrial morphology and function. These effects were achieved by promoting mitochondrial biogenesis and inhibiting mitochondrial fragmentation through the SIRT1-DRP1/PGC-1α pathway. The findings provide new evidence supporting the use of curcumin as a potential therapeutic agent for SCM.This study investigates the effects of curcumin on septic cardiomyopathy (SCM) and explores its potential mechanisms. Curcumin, a polyphenolic compound with antioxidant, anti-inflammatory, and cardiovascular protective properties, was tested in both in vivo and in vitro models of sepsis. The study found that curcumin significantly improved survival rates, cardiac function, and reduced inflammatory responses in sepsis-induced mice. Mechanistically, curcumin activated sirtuin 1 (SIRT1), increased the expression of mitochondrial biogenesis-related genes (Pgc1α, Tfam, and Nrf2), reduced dynamin-related protein 1 (DRP1) translocation to mitochondria, and restored mitochondrial morphology and function. These effects were achieved by promoting mitochondrial biogenesis and inhibiting mitochondrial fragmentation through the SIRT1-DRP1/PGC-1α pathway. The findings provide new evidence supporting the use of curcumin as a potential therapeutic agent for SCM.