Biopolymer nanocomposites based cellulose acetate, hydroxyapatite, bioglass and zirconia have been synthesized using a solvent casting method for biological interest. Different concentrations of zirconia have been prepared and characterized. The results clarified that the increase in the concentration of ZrO2 improves the mechanical properties as the microhardness becomes 405.5 MPa with 11.76 wt% of ZrO2 instead of 69.4 MPa with no ZrO2 content. Additionally, introducing ZrO2 into the nanocomposite improve its wettability as contact angle is decreased from 65° for the pure sample to 38.4° for the composite with 1.3 wt% ZrO2. Moreover, the agar diffusion antimicrobial study showed that only sample with 3.22 wt% of ZrO2 nanocomposite has mild inhibitory responses against Pseudomonas aeruginosa, whereas the rest of the formula does not have any antibacterial activity. Furthermore, in-vitro cytotoxicity of the nanocomposite samples on the Vero cell line was also studied. These Vero normal cells were incubated with test materials for 72h at 37°C/ 5% CO2, and cell viability was detected using the sulforhodamine B (SRB) assay. All Nanocomposites were mildly to non-cytotoxic to Vero cells with high concentration compared with inhibitory effect of doxorubicin, which was added with 10-fold lower than nanocomposites. With these findings, the proposed nanocomposite could be used in dental applications.