Poly (lactic acid)/silicone rubber (PLA/SR) blends were reinforced with (3-aminopropyl) triethoxysilane-functionalized titanium dioxide nanoparticles, and the effect of the virgin (TDO) and functionalized (FTDO) nanoparticles was investigated in the presence and absence of compatibilizer. The results demonstrated that the functionalization of TDO had no negative effect on the morphology of the blends, and no aggregation was seen in the blends containing TDO and FTDO. Furthermore, nanoparticles were localized at the interface of PLA and SR. Adding TDO in the PLA/SR blends increased the mechanical properties. The same trend was observed after incorporating the compatibilizer and FTDO.Additionally, a good agreement was seen between the theoretical and experimental mechanical properties values. Moreover, introducing SR diminished the crystallinity of PLA, and further reduction was observed by adding TDO, FTDO, and compatibilizer. Also, the modification of TDO did not affect the crystallinity of the blends. Incorporating 1 and 2 phr TDO to the blends increased the thermal stability while diminishing with 3 phr TDO. In addition, FTDO improved thermal stability. The antibacterial test indicated that the higher nanoparticles content, the better the antibacterial properties.