A growing concern around the world is the number of people that are suffering from food protein allergies, especially among infants and young children. One potential approach is to block IgE binding epitopes of the protein allergen via the Maillard reaction with polysaccharides to decrease the allergy potential. Dairy infant formula is often formulated to a high proportion of whey proteins, and if infants are sensitive to whey proteins then hydrolysis of whey proteins is often used. The goal of this research was to reduce the immunogenicity of whey protein isolate (WPI) by conjugating WPI with dextran (DX). During this study, the effect of the molecular weight (M_W) of DX, ranging from 1 to 2000 kDa, on the immunogenicity of WPI-DX were explored. Our data indicated that the WPI to DX molar ratios in the conjugates made from DX with M_W values of 1 (G1), 3.5 (G3.5), 10 (G10), 150 (G150), 500 (G500), and 2000 kDa (G2000) were 1:4, 1:3, 1:2, 1:1.5, 1:1, and 1:1, respectively. With the increase in the M_W of DX, the M_W values of the corresponding conjugates were also increased, as determined by size exclusion chromatography with multiangle laser light scattering. The immunogenicity of conjugates were evaluated by IgE binding capacity of conjugates incubated with serum from blood samples obtained from patients with cow’s milk protein allergy. Our results showed that WPI-DX conjugates have a lower WPI-specific IgE binding capacity than native WPI, with the lowest IgE binding capacity obtained in G10 conjugate, demonstrating that glycation via Maillard reaction did significantly reduce the immunogenicity of WPI. Furthermore, atomic force microscopy images suggested that conjugation of WPI with small M_W dextran resulted in greater surface coverage on the protein compared with large dextran conjugates, hence significantly reducing protein immunogenicity by creating steric hindrance that limited IgE binding.