Myricetin (MYR) is a flavonoid with favorable biological activities. In this study, MYR oxidation products (MYRox) were generated through enzymatic oxidation of MYR using horseradish peroxidase. The results showed enzymatic oxidation enhanced the water solubility and antibacterial activity against Staphylococcus aureus (S. aureus) of MYR. Further experiments showed the antibacterial effects of MYRox were conferred by MYR organic phase oxidation products (MYRoo). Both MYR and MYRoo could disrupt the cell membrane integrity, bind to the genomic DNA, affect protein synthesis and degradation, and alter the ROS levels in S. aureus. However, they exerted these effects with different strengths and ways. Finally, MYR or MYRoo can be used as an inhibitor against S. aureus in the cabbage food system, with MYRoo having better effect. This study demonstrated that enzymatic oxidation is an effective approach to improve the water solubility and antibacterial activity of MYR, enhancing its potential application in food preservation.