To date, approximately 30-50% of food is wasted from post-harvesting to consumer usage. Typical examples of food by-products are fruit peels and pomace, seeds, and others. A large part of these matrices is still discarded in landfills, while a small portion is valorized for bioprocessing. In this context, a feasible strategy to valorize food by-products consists of their use for the production of bioactive compounds and nanofillers, which can be further used to functionalize biobased packaging materials. The focus of this research was to create an efficient methodology for the extraction of cellulose from leftover orange peel after juice processing and for its conversion into cellulose nanocrystals (CNCs) for use in bionanocomposite films for packaging materials. Orange CNCs were characterized by TEM and XRD analyses and added as reinforcing agents into chitosan/hydroxypropyl methylcellulose (CS/HPMC) films enriched with lauroyl arginate ethyl (LAE®). It was evaluated how CNCs and LAE® affected the technical and functional characteristics of CS/HPMC films. CNCs revealed needle-like shapes with an aspect ratio of 12.5, and average length and width of 500 nm and 40 nm, respectively. Scanning electron microscopy and infrared spectroscopy confirmed the high compatibility of the CS/HPMC blend with CNCs and LAE®. The inclusion of CNCs increased the films' tensile strength, light barrier, and water vapor barrier properties while reducing their water solubility. The addition of LAE® improved the films' flexibility and gave them biocidal efficacy against the main bacterial pathogens that cause foodborne illness, such as Escherichia coli, Pseudomonas fluorescens, Listeria monocytogenes, and Salmonella enterica.