Aim . The aim of this study was to elucidate the potential mechanism of Rg1 in alleviating hepatic ischemiareperfusion (HIRI) through the mitophagy pathway. Methods . The HIRI rat models were established and divided into 4 groups: the sham group, sham+Rg1 group, ischemia/perfusion (I/R) group and I/R+Rg1 group. Then the activities of aspartate transaminase (AST) and alanine aminotransferase (ALT) were detected by automatic serum analyzer. Meanwhile, cell apoptosis and changes in liver tissues were checked by TUNEL assay and histopathological analysis, respectively. The relative protein levels were detected by western blotting. Subsequently, cell counting Kit-8 assay and cytometric analysis were used to investigate cell viability and apoptosis of liver cells. Finally, the time points of the strongest mitochondrial autophagy were explored and the mitochondrial morphology was observed by the mitochondrial transmembrane potential (MMP) in vivo and in vitro. Results . The mitophagy aggravated hepatocyte damage during liver I/R in vivo. In addition, Rg1 alleviated liver damage after liver I/R, maintained the stability of MMP and inhibited mitochondrial autophagy and signaling pathways during liver I/R in vivo. Furthermore, Rg1 could effectively increase cell viability, inhibit cell apoptosis and stabilize MMP after OGD/R injury in vitro Moreover, Rg1 exerted its protective effect on HIRI by regulating the PINK1/Parkin signaling pathway and the mitochondrial autophagy. Conclusion . Rg1 could further improve its mechanism of alleviating HIRI in apoptosis and autophagy, 2 types of regulated programmed cell death via the mitochondrial pathway (Altern Ther Health Med. 2023;29(3):16-25).