In the present study, the piezoelectric aluminum nitride (AlN)/tantalum (Ta) (PAT) thin film was investigated as a biocompatible film and osseointegrated with biomedical devices such as implants. The stress variation on the interaction of cells with the PAT surface was investigated using osteoblast-like cells (MG-63) and fibroblast cells (NIH3T3). A singular behavior was observed on the PAT film with a (002) texture, in which the MG-63 cells were more dispersed and displayed longer and more filopodia than the NIH3T3 cells. Moreover, the MG-63 cells showed ingrowth, adherence, and proliferation on the PAT film surface. The MG-63 cells had more obvious stress variation than the NIH3T3 cells in the differentiation and proliferation. The mechanobiological reaction to cell differentiation and proliferation not only caused osseointegration, but also reduced the surface activation energy, thus enhancing bone remodeling. The formation of a nanopolycrystalline PAT film is believed to enhance the mechanobiological effect, promoting osseointegration.