Active packaging manufactured with biopolymers extracted from agri-food waste is one of the most innovative and eco-sustainable strategies for maintaining food quality. However, biopolymers often present poor performances, which hinders their competitiveness compared with plastics. This work focused on developing and optimizing a natural polymeric blend produced by solvent casting based on zein and chitosan to improve the pure biopolymers’ properties. The best results were obtained by blending zein and chitosan in a 1:2 weight ratio. The films were characterized in terms of morphology, mechanical and oxygen barrier properties, thermal stability, transparency and wettability. The blend production allowed us to obtain lower brittleness and lower stiffness materials compared with pure polymer films, with oxygen permeability values two orders of magnitude lower than pure zein, better optical properties with respect to pure chitosan and good thermal stability. The wettability properties of the blend did not result in being altered with respect to the single polymer, which was found to have hydrophilic behavior, highlighting the strong influence of glycerol used as a plasticizer. The results suggested that the polymer blending strategy is a viable and cost-effective method for producing packaging materials as alternatives to plastics.