There is limited information about how the co-digestion of different food matrices can affect the digestibility, bioaccessibility, and hence, the effectiveness of their health beneficial compounds, such as polyphenols. This work aimed to study the effect of the co-digestion of a whole-wheat pasta dish with a glass of red wine on their antioxidant properties. Changes in the total polyphenol content (TPC) by Folin Ciocalteu, phenolic profile by HPLC-ESI-MS/MS, and in vitro antioxidant capacity (AC) by FRAP and ABTS methods were studied before and after simulated gastrointestinal digestion (GID). A final stage of dialysis was also included to study the fraction of compounds potentially bioaccessible. The digestions of pasta and red wine separately were also investigated. The results obtained showed that the phenolic profile and AC changed throughout GID. Additionally, the co-digestion increased the AC by ABTS of the bioavailable fraction with respect to the sum of the food digested separately. Differences in the bioavailability of phenolics were also found, with an increase of 4 compounds characteristic of pasta and 4 of wine. This study shows that the co-ingestion of pasta with wine improves the antioxidant properties of these foods and points out the importance of co-digestion studies to don’t underestimate these properties.