<p>This work studied the transformation of whey protein isolate (WPI) in a thermoplastic material (WPIT) with the addition of the antioxidant α-tocopherol, as known as vitamin E, and the plasticizer polyethylene glycol (PEG). The miscibility of the components was evaluated using the Flory-Huggins interaction parameters. WPIT samples were formulated following a Design of Experiments (DOE) factorial design 2² with a central point with vitamin E and PEG content as factors. Samples were prepared using a heat treatment for denaturation, dried in a vacuum oven, lyophilized, and cryogenically milled. The final properties obtained were evaluated by Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), Thermogravimetry (TGA), and moisture content. The results showed miscibility between PEG and WPI and partial miscibility between the pairs α-tocopherol/WPI and PEG/α-tocopherol. PEG and vitamin E exhibited a plasticizing effect on the polymer chains, reducing the contribution of extended β-sheet structures in the secondary structure of the protein, increasing the presence of α-helices, and decreasing the glass transition temperatures related to the protein. Vitamin E improved the thermal stability of WPIT, but its excess may lead to a pro-degradant effect. The amount of α -tocopherol and PEG influenced the moisture content. The hydrophobicity of vitamin E strongly influenced moisture content, keeping it low for samples with higher content of this additive.</p>