Antimicrobial packaging is one of the most promising active packaging systems for controlling spoilage and pathogenic microorganisms. In this work, the intrinsic antimicrobial properties of chitosan (CH) were combined with the excellent thermoplastic and film-forming properties of sodium caseinate (SC) to prepare SC/CH film-forming solutions and films. The antimicrobial effectiveness of SC, CH, and SC/CH coatings on the native microfloras of cheese, salami, and carrots was evaluated. In vitro assays through the test tube assay indicated that the most significant antimicrobial effect was achieved by CH and SC/CH solutions on carrot and cheese native microfloras. SC film-forming solutions did not exert antimicrobial activity on any of the native microflora studied. SC, CH, and SC/CH films stored in controlled environments showed that the retention of the antimicrobial action was observed until 5-d storage, at 65% relative humidity in both temperatures (10 °C and 20 °C). In vivo assays were also performed with SC, CH, and SC/CH applied as coatings or wrappers on the 3 food substrates. CH and SC/CH applied at both immersion and wrapper exerted a significant bactericidal action on mesophilic, psychrotrophic, and yeasts and molds counts, showing the 3 microbial populations analyzed a significant reduction (2.0 to 4.5 log CFU/g). An improvement of the bactericidal properties of the CH/SC blend respect to those of the neat CH film is reported. The ionic interaction between both macromolecules enhances its antimicrobial properties. Practical Application: The continuous consumer interest in high quality and food safety, combined with environmental concerns has stimulated the development and study of biodegradable coatings that avoid the use of synthetic materials. Among them, edible coatings, obtained from generally recognized as safe (GRAS) materials, have the potential to reduce weight loss, respiration rate, and improve food appearance and integrity. They can be used in combination with other food preservation techniques in order to extend the effectiveness of the food preservation chain. Moreover, antimicrobial films and coatings have innovated the concept of active packaging and have been developed to reduce, inhibit, or delay the growth of microorganisms on the surface of food in contact with the package. The use of antimicrobials packaging films to control the growth of microorganisms in food can have a significant impact on shelf-life extension and food safety. In addition, antimicrobial films can be prepared by the combination of inherent antimicrobial materials (that is, CH), with good film-forming protein-based ones (that is, SC). Therefore, the objective of this work is to study the performance of 2 biodegradable and edible biopolymers and their combination as natural packages for selected food products.