AbstractNanoparticles of zinc oxide (ZnO), polyhedral oligomeric silsesquioxane (POSS), and their hybrids were added to polylactic acid (PLA) using solution casting process at different weight percentages of the nanoparticles (1, 3, and 5 wt%) to form developed nanocomposites for food packaging applications. According to FTIR and XRD studies, both nanoparticles displayed fair chemical interactions with the PLA matrix. Furthermore, morphological investigations (SEM‐EDS) revealed that POSS, ZnO, and their hybrids were uniformly dispersed into the matrix despite some microaggregations at 5 wt% of nanoparticles, especially for those containing POSS. Moreover, adding 1 wt% of POSS to PLA increased its tensile strength and modulus by 20% and 149%, respectively, while decreasing the elongation‐at‐break by 54%. In addition, the tensile strength, tensile modulus, and elongation‐at‐break of PLA all increased by 7.5%, 28.7%, and 162%, respectively, with the addition of 1 wt% ZnO. Contact angle and surface free energy experiments demonstrated that after incorporating ZnO and POSS into the PLA matrix, the hydrophobicity of the samples increased, and POSS nanoparticles could minimize bacterial adherence effectively. In addition to the antibacterial properties of ZnO and POSS nanoparticles, increasing the concentration of hybrid nanoparticles up to 5 wt% expanded the bacteria's inhibitory zone, particularly in the case of Gram‐positive bacteria (Staphylococcus aureus). Finally, the hybrid nanocomposites exhibited both balanced mechanical characteristics and promising antibacterial activity compared with those with ZnO and POSS alone.