Peanut allergy is usually lifelong and accidental exposure impose formidable risk. The aim of this study was to assess the capacity of peanut proteins complexed to polyphenol extracts to reduce allergic response in C3H/HeJ mice. Mice were sensitized to peanut flour followed by exposure to amino acid diets fortified with peanut protein-polyphenol aggregates of either with low (15%; w/w) or high (40%; w/w) complexation ratios of blueberry (BB-Low and BB-High) and cranberry (CB-Low and CB-High) extracts. Treatment groups on diets with high complexation ratios of blueberry and cranberry aggregates showed significant reduction in peanut specific plasma Immunoglobulin E (IgE). Western blot analysis of spleen lysates showed CD63 protein expression was reduced in a dose-dependent manner in blueberry and cranberry complexed peanut protein supplemented diet groups. Our results demonstrate for the first time that complexation of polyphenols to peanut flour can potentially lower plasma IgE of peanut-sensitized C3H/HeJ mice.