Food packaging plays a significant role in the food industry and has an impact on a number of factors related to the food product and the consumer. Works on biodegradable polymers have been carried out in an effort to solve the issue of the environment being negatively impacted by the growing use of synthetic polymers. The objective of the present work is to compose bionanocomposites that can be used as packaging materials. Polylactic acid (PLA) loaded with (2% w/w) titanium dioxide nanoparticles (TiO2-NPs) nanoparticles (PLA/TiO2) bionanocomposite was successfully prepared. Then, CuO-TiO2 nanocomposite was prepared and added with different concentrations (1, 3, and 5% w.) to the PLA matrix to fabricate PLA/CuO-TiO2 bionanocomposites. Furthermore, the fashioned PLA/CuO-TiO2 bionanocomposites were evaluated via Fourier-transform infrared spectroscopy (FTIR), scanning electron microscope (SEM), transmission electron microscope (TEM), oxygen transmission rate (OTR), water vapor transmission rate (WVTR), and X-ray diffraction pattern (XRD). Moreover, the thermal, mechanical, and antimicrobial properties of the PLA bionanocomposites films were improved upon loading CuO-NPs (1.0, 3.0, and 5.0%) with the supported TiO2-NPs (2% w/w) compared by pure PLA. Moreover, the obtained result confirmed that the prepared PLA/CuO-TiO2 bionanocomposites were monitored seeking enhanced PLA bionanocomposites to be applied as packaging materials.