In this research, first, ZnO nanorods were synthesized by hydrothermal method and characterized in terms of morphological and structural properties by means of field emission scanning electron microscopy, Fourier transform infrared, and X-ray diffraction techniques. Subsequently, polylactic acid/ZnO, polylactic acid/TiO2, and polylactic acid/ZnO/TiO2 nanocomposites with different percentages of nanoparticles and two different types of ZnO morphologies were prepared and their microstructural, optical, mechanical, hydrolytic degradation, and antibacterial properties were investigated. Field emission scanning electron microscopy results of polylactic acid/ZnO and polylactic acid/TiO2 samples showed a proper dispersion and nanoparticle distribution for low percentages (up to 5 wt%) and increased aggregation for the higher percentages. Besides, a large increase in the aggregation tendency was observed for combined nanoparticles (polylactic acid/ZnO/TiO2 nanocomposites). Results of the tensile test, the UV–Vis absorption tests, and the hydrolytic degradation tests of the samples showed an enhanced mechanical (approximately 55% increase in the presence of 3–5 wt% of nanoparticles) and light absorption and degradation (approximately 85% increase in the presence of 3–10 wt% of nanoparticles) for the polylactic acid by incorporating nanoparticles. It was also observed that, in addition to the quality of dispersion and distribution of nanoparticles in the polymeric matrix, the type of morphology of nanoparticles can contribute to the improvement of these properties. The cylindrical morphology of ZnO played a greater role on improving the polylactic acid mechanical properties compared to the spherical ZnO morphology (approximately 20%). On the contrary, the increased polylactic acid optical properties and degradation with ZnO spherical morphology were more pronounced (approximately 60%). Interestingly, when both ZnO and TiO2 were added, a synergistic effect in the case of UV-shielding and degradation rate and alternatively, a detrimental effect on the mechanical properties were detected. (The polylactic acid optical properties increased by about 17% and its degradation more than doubled.) Furthermore, the antibacterial activity of polylactic acid was investigated against the two Gram-positive Listeria monocytogenes and Gram-negative bacteria Escherichia coli by incorporating nanoparticles. The results indicated that as the nanoparticle percentage increases, the antibacterial activity steadily increases.