Research Background: Amaranth ( Amaranthus hypochondriacus ) flour produces films with excellent barrier properties against water vapor, allowing food preservation, but the mechanical properties are poor compared to synthetic films. One strategy to improve these properties is the incorporation of nanoparticles. The particles can also serve as a vehicle for the addition of antioxidant agents into the films. The objective of this work is to optimize the formulation for the preparation of amaranth flour films treated with antioxidant chia ( Salvia hispanica L.) extract-loaded chitosan particles using response surface methodology (RSM)., Experimental Approach: Chitosan nanoparticles with the extract were synthesized by ionic gelation, and the films were made by the casting method. Three independent variables were assigned: amaranth flour (4-6%), glycerol (25-35%) and chitosan nanoparticles loaded with the chia extract (0-0.75%). We then evaluated the physical (thickness), mechanical (tensile strength, Young´s modulus and elongation), barrier (water vapor permeability, moisture and water solubility) and antioxidant properties of the films. The experimental results of the properties were analyzed using a Box-Behnken experimental design generating 15 runs with three replicates at the central point., Results and Conclusions: Second and third order polynomial models were obtained from the ANOVA analysis of the evaluated responses, and high coefficients of determination were found (0.91-1.0). The water vapor permeability of the films was 0.82-2.39·10 -7 (g·mm)/(Pa·s·m 2 ), tensile strength was 0.33-1.63 MPa and antioxidant activity 2.24-5.65%. The variables had different effects on the films: glycerol negatively affected their properties, and the permeability values increased with increased amaranth flour content. The nanoparticles improved the mechanical, barrier and antioxidant properties of the films compared to the films without nanosystems. The optimal formulation was 4% amaranth flour, 25% glycerol and 0.36% chitosan nanoparticles. The optimized films had better mechanical (1.62 MPa) properties, a low water vapor permeability value (0.91·10 -7 (g·mm)/(Pa·s·m 2 )) and moderate antioxidant activity (6.43%)., Novelty and Scientific Contribution: The results show the effect of chitosan nanoparticles on the properties of amaranth flour films for the first time. The resulting equations are useful in the design of food packaging., Competing Interests: CONFLICT OF INTEREST The authors declare no conflict of interest with respect to authorship, research and/or publication of this paper.