ABSTRACT: The formations of glycerol (Gly)-plasticized whey protein isolate (WPI)–hydroxypropylmethylcellulose (HPMC) films, blended using different combinations and at different conditions, were investigated. The resulting WPI: Gly-HPMC films were analyzed for mechanical properties, oxygen permeability (OP), and water solubility. Differences due to HPMC quantity and blend method were determined via SAS software. While WPI: Gly and HPMC films were transparent, blend films were translucent, indicating some degree of immiscibility and/or WPI–HPMC aggregated domains in the blend films. WPI: Gly-HPMC films were stronger than WPI: Gly films and more flexible and stretchable than HPMC films, with films becoming stiffer, stronger, and less stretchable as the concentration of HPMC increased. However, WPI: Gly-HPMC blended films maintained the same low OP of WPI: Gly films, significantly lower than the OP of HPMC films. Comparison of mechanical properties and OP of films made by heat-denaturing WPI before and after blending with HPMC did not indicate any difference in degree of cross-linking between the methods, while solubility data indicated otherwise. Overall, while adding HPMC to WPI: Gly films had a large effect on the flexibility, strength, stretchability, and water solubility of the film polymeric network, results indicated that HPMC had no effect on OP through the polymer network. WPI–HPMC blend films had a desirable combination of mechanical and oxygen barrier properties, reflecting the combination of hydrogen-bonding, hydrophobic interactions, and disulfide bond cross-linking in the blended polymer network.