Polyphenols are specialized metabolites produced by plants with a well-documented overall health effect. They are also described in the literature to interact with proteins, with possible impacts on protein functionality or digestibility. For example, polyphenols have a strong affinity for whey proteins such as alpha-lactalbumin and beta-lactoglobulin. However, the fate of polyphenols-protein complexes in the digestive tract is not fully described. In order to tackle this question, we examined the interactions between alpha-lactalbumin and two polyphenols at pH 4: epigallocatechin gallate (EGCG) and procyanidin B2. The objective was to evaluate the impact of the polyphenol structure, the protein concentration and the polyphenol:protein molar ratio on these interactions. Several techniques have been used such as turbidity measurement, isothermal titration calorimetry (ITC) and fluorescence spectroscopy. We observed overall greater turbidity with EGCG than with procyanidin B2, and an increase of turbidity with increasing protein concentration and polyphenol/protein ratio. We also detected by ITC an interaction of alpha-lactalbumin with EGCG and no interaction with procyanidin B2 under the same experimental conditions (Figure 1). We observed a decrease in fluorescence intensity with PB2 by fluorescence spectroscopy, but very weak compared to EGCG. Our preliminary results indicate that EGCG has a stronger affinity for alpha-lactalbumin compared to procyanidin B2. The presence of the galloyl group is probably determinant in the higher affinity of EGCG towards the model protein (Poncet-Legrand et al. 2006). The perspective of this work is to study the fate of these polyphenol-protein complexes in the digestive tract, first in the mouth by introducing a salivary protein rich in proline (PRP) with very strong affinity towards tannins, and second in the gastrointestinal tract by simulating the digestive conditions using the in vitro protocol INFOGEST. Understanding the evolution of these complexes could provide information on their possible consequences on the bioaccessibility of food proteins and/or polyphenols.