Proteins and phenolic compounds can interact and form soluble and insoluble complexes. In this study, the complexation of whey protein isolate (WPI) with caffeic acid (CA) or (-)‑epigallocatechin‑3‑gallate (EGCG) is investigated as a strategy to attenuate oral sensitization in C3H/HeJ mice against WPI. Treatment with WPI-CA reduced the levels of IgE, IgG1, IgG2a and mMCP-1 in serum of mice measured by ELISA. This might be related to CD4+LAP+Foxp3+ T and IL-17A+CD4+ T (Th17) cell activation, evidenced by flow cytometry of splenocytes. Treatment with WPI-EGCG, in turn, decreased the levels of IgG2a and mMCP-1 in serum of mice, possibly by the modulation of Th1/Th2 response and the increase of CD4+ Foxp3+ LAP- T and IL-17A+CD4+ T (Th17) cell populations. In conclusion, WPI-CA and WPI-EGCG attenuated oral sensitization in C3H/HeJ mice through different mechanisms. We consider that the complexation of whey proteins with CA and EGCG could be a promising strategy to induce oral tolerance.