Driven by the growing eco-awareness, bio-based polymers have been widely explored lately. In spite of important scientific breakthroughs, widespread technological usage is limited sometimes by performance mismatch with the currently used materials and often by the lack of scalability towards large-scale production. This study focuses on the combination of polysaccharides and proteins into a bilayer design that was shaped into flat films in a scaled-up fashion by continuous casting. The objective was the study the production parameters and the effect of the composition of the bilayer film, considering both electrostatic interactions and the nature of the protein. To achieve this, carboxymethylcellulose (CMC) served as a supporting layer coated by either a gelatin (GEL) or a casein (CA) layer, all from aqueous solutions. The electrostatic interactions were assessed by depositing gelatin solutions with positive (pH 3), neutral (pH 4.5), and negative (pH 8) charges onto the anionic CMC layer. The produced films were self-supporting, transparent, and uniform as far as thickness. The protein nature and solution pH considerably affected both viscosity and shear stress. GEL/CMC bilayer films showed better adhesion than CA/CMC films owing to protein organization and exposure of functional groups presenting different affinities with CMC. The mechanical resistance depends on interlayer adhesion to ensure efficient stress transfer. Uniaxial tensile tests showed two failure steps and evidenced the poorest strength (12 MPa) and elongation at break (4%) of GEL/CMC films from neutral solutions. The CA/CMC films had tensile strengths (ca. 20 MPa) similar to those produced with gelatin at pH 3 and 8, but the elongation at break was two times lower (4%). The GEL/CMC films appeared to have proper interlayer adhesion, while the CA/CMC films easily delaminated when handled. A significant decrease in the water vapor permeability of the GEL/CMC films was observed relative to the control monolayer films, behavior that was independent of pH. The opposite behavior was observed for CA/CMC films, suggesting that films comprising casein boast greater affinity to moisture. Such behavior was corroborated by the swelling assays, in which the CA/CMC films showed 25% greater water absorption than GEL/CMC films. The interactions between protein and CMC, as analyzed by QCM-D, indicate that the nature and surface charge can modulate the polymeric affinity. It is concluded that the combination between CMC and protein depends on the nature of the protein, which includes the structural organization and the exposure of functional groups, in addition to the electrostatic interactions that can affect the stress transfer between the layers.