Objective:This study aimed to investigate the protective effect of dihydromyricetin (DHM) and its derivatives on oxidative damage of hepatocytes.Methods:The hydrogen peroxide damage model of L02 cells was established. DHM derivatives with different lipophilicity were obtained by enzymatic acylation of DHM. The levels of reactive oxygen species (ROS), lactate dehydrogenase (LDH), malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), and mitochondrial membrane potential and Caspase 3 were measured to evaluate the protective effect of DHM and its derivatives on damaged hepatocytes.Results:Except for 3-O-lauroyl-DHM, the level of reactive oxygen species (ROS) the release of lactate dehydrogenase (LDH) and the level of malondialdehyde (MDA) and Caspase 3 in damaged hepatocytes treated with other derivatives decreased significantly, while the levels of antioxidant enzymes and the mitochondrial membrane potential increased. Of which, 3-O-octanoyl-DHM showed the best protective effect.Conclusion:Dihydromyricetin derivatives with medium chain length have better liver protection effect.