The effect of procyanidin dimer B3, a common food tannin, on the digestion of gliadin proteins was investigated by monitoring the changes in the immunogenic peptides produced during in vitro digestion and immunoreactivity. Interaction studies between procyanidin dimer B3, gluten proteins and/or digestive enzymes were performed by SDS-PAGE. The effect of procyanidin B3 on the enzymatic activity of trypsin, chymotrypsin and pancreatin was evaluated. The differences in the number and nature of immunogenic peptides released during digestion were identified by mass spectrometry. Briefly, the enzymatic activity of gastrointestinal enzymes was only slightly affected but a significant decrease in the immunological properties of the peptides produced during digestion was observed. Overall, although further studies are needed, the interaction between polyphenols and gluten proteins clearly influences gluten protein digestion and immunogenicity, thus suggesting that the consumption of dietary polyphenols can significantly affect the degree of celiac disease downstream immune reactions.