In order to screen out lactic acid bacteria that can protect cells from oxidative stress damage, five different lactic acid bacteria were fermented to obtain fermentation extracts, and the effectiveness and mechanism of the obtained fermentation broth was tested at the biochemical, cellular, and molecular levels. Results showed that the five kinds of lactic acid bacteria fermentation broth extracts have good ability to scavenging ?OH and O2-?. The Lactobacillus plantarum fermented extract (FE1) had the strongest scavenging effect on the two free radicals as 10g/L FE1 can scavenge 49.14% of hydroxyl radicals and 73.99% of superoxide anions. FE1, Lactobacillus paracasei fermented extract 2 (FE2) and Lactobacillus acidophilus fermented extract (FE3) can significantly improve the survival rate of cells (p< 0.05) and the activity of glutathione peroxidase (p<0.05), while reducing the intracellular reactive oxygen species content (p<0.05). Among them, FE1 significantly increased the activity level of catalase and superoxide dismutase in the cell and the total antioxidant capacity of the cell (p<0.05). The results of molecular biology experiments showed that the FE1 can promote the up-regulation of antioxidant genes Sirt1 and activate the key regulatory gene β-catenin in the Wnt/β-catenin pathway, thereby up-regulating the expression of MP30, FoxO3a, and Tbx3 antioxidant genes to enhance its antioxidant activity ability. The good antioxidant effect of the fermentation extract of Lactobacillus plantarum can slow down the oxidative damage of skin cells stimulated by H2O2.