In recent years, red wine drinking has become more popular in China owing to its antioxidant effects. However, the key antioxidant compounds and their action mechanisms of Chinese red wines are still unclear. Herein, the antioxidant activities and chemical compositions of 45 Chinese Cabernet Sauvignon red wine samples were determined using chemical antioxidant assays and an UHPLC-QTOF-MS-based untargeted metabolomics method. The key antioxidant compounds in red wines and potential action mechanisms were revealed by integrating network pharmacology and molecular docking approaches. Results showed that there are 8 key antioxidant compounds in the red wine samples. These compounds are involved in several metabolic pathways in the body, particularly PI3K/AKT. What's more, they bind to the core antioxidant targets through hydrogen bonding and hydrophobic interaction. Among them, myricetin, laricitrin, 2,3,8-tri-O-methylellagic acid and AKT1 have the highest binding energies. This study could provide the theoretical basis for further investigation of physiological activities and functions of Chinese red wines. Display omitted •Chinese Cabernet Sauvignon red wines showed to have strong antioxidant activities.•8 key antioxidant compounds in Chinese red wines were identified by untargeted metabolomics.•5 core antioxidant targets of active compounds were screened by network pharmacology.•PI3K/AKT was one of the most represented metabolic pathways of antioxidant compounds.•Myricetin, laricitrin, 2,3,8-tri-O-methylellagic acid and AKT1 have the highest binding energies.