The oxidation of wine may be beneficial or harmful to its quality. On the one hand, controlled oxidation can lead to the development of desirable sensory characteristics for red wine, such as enhanced color stability. Alternatively, oxidation can lead to white wine browning and a decrease in fruity aromas, and the development of an off flavor and wine polyphenols are also involved. The presence of glutathione (GSH) can help mitigate the negative effects of oxidation by acting as a protective antioxidant. In order to better understand the antioxidant role played by GSH, wine polyphenols oxidation experiments by electrochemical means in the presence of GSH were carried out. The oxidation behavior of polyphenols representing different phenolic classes commonly found in wines, including protocatechuic acid (PCA), caffeic acid (CAF), epicatechin (EC), and rutin (Ru), was investigated using cyclic voltammetry and bulk electrolysis. We identified the oxidation products and reaction pathways of these polyphenols using ultra-high-performance liquid chromatography coupled with mass spectrometry (UPLC-MS), in both the absence and the presence of glutathione (GSH). UPLC-MS was utilized to demonstrate that, in the presence of glutathione (GSH), the four molecules were subjected to electrochemical oxidation, resulting in the formation of mono-and bi-glutathione conjugates. A two-electron oxidation process combined with the removal of two protons is the first step in transforming polyphenol molecules. As a result, the corresponding quinone is formed. The quinone can then be reduced back to its original form by glutathione (GSH), or it can interact further with GSH to produce mono-and bi-glutathione conjugates. These results contribute to understanding and predicting the oxidative degradation pathway of polyphenols in wine. Understanding this process seems important for winemakers to control and optimize the sensory characteristics of their wines.