Bio-based plastics emerged as eco-friendly and resource-efficient substitutes for petroleum-based counterparts. Despite the continuous efforts to develop these alternatives, their inferior performance, most notably mechanical and moisture barrier aspects, limits their application. Material hybridization, like polymer blending and nanocomposite technology, are among the methods employed to improve the properties of bioplastics. This present work focuses on synthesizing bioplastic films with 30/70, 50/50, and 70/30 chitosan to cellulose (CH/CE) percent weight ratios. FTIR analysis of the blend films revealed interaction between NH2 and OH, confirming the compatibility between chitosan and cellulose. Analysis of variance showed increasing cellulose content significantly (p < 0.05) enhanced the resistance to swelling. The 30/70-CH/CE film exhibited the least swelling, which is 65.5% lower than the pure chitosan film. Moreover, copper oxide nanoparticles (CuO NPs) were prepared as reinforcement due to its hydrophobicity. Structural and morphological analyses of hydrothermally synthesized CuO nanoparticles confirmed monoclinic and urchin-like structure. Varying amounts of CuO NPs, i.e., 1%, 3%, and 5% w/v were added to the 30/70-CH/CE films to further enhance the moisture barrier properties. The best barrier performance was attained at 5% w/v, indicated by the smallest % swelling (93.25%) and largest contact angle measurement (89.32°). This could be related to the morphological change from fibrous to smoother film surface with increasing amount of CuO NPs. Results suggest the potential of the chitosan/cellulose polymer blend and the copper oxide nanoparticle-reinforced films for moisture barrier applications.