Extracting mechanical properties of living cells by Atomic Force Microscope (AFM) can cause cell destruction due to uncontrolled forces. In this regard, the reaction of healthy (MCF-7) and cancerous (MCF-10A) breast cells and human Red Blood Cells (RBCs) to contact force was simulated by using different contact theories and applying time-dependent mechanical models. To validate the simulation results, the topography test and nanomanipulation of MCF-7 and MCF-10A using AFM was implemented. Experimental data showed that the average maximum diameter of MCF-7 and MCF-10A is 25.24 and 12.06 μm, respectively. Furthermore, the elastic modulus of the MCF-7 and MCF-10A cells was calculated in the range of 1.23 ± 0.02 kPa, and 1.17 ± 0.02 kPa, respectively. In addition, the contact theories were developed for application in the case of different geometries, and utilized for modeling the contact mechanics of human RBCs. The results showed that Hertz and DMT theories accurately calculate the contact behavior of living cells in small deformations; However, in case of large contact deformations, Tatara and Chang's theories provide more accurate results. Furthermore, the effect of RBC geometry on the contact parameters is negligible due to the significant difference in the dimensions of RBCs in comparison with AFM-tip.