Correlation between microscopy, spectroscopy and molecular modeling is essential for elucidating reactivity of biomaterials based on their electronic; physical and surface properties. Consequently, FTIR microspectroscopy (FTIRM) was used to study Poly(N-vinylpyrrolidone) (PVP) and PVP-CaCO3 films prepared via solution casting method. FTIR spectra confirmed the physical interaction between PVP and CaCO3, thus indicating the availability of the functional groups of both compounds for further interaction. DFT molecular modeling calculations at B3LYP/6-31G (d, p) basis set were performed on PVP, CaCO3 and four proposed schemes of interaction between both of them, and the structure's stability was examined in terms of total energy, while electronic properties were investigated in terms of total dipole moment, HOMO-LUMO band gap energy (ΔE), and molecular electrostatic potential maps (MESP). QSAR calculations were also performed to monitor the reactivity of the four proposed PVP-CaCO3 interactions. The obtained FTIRM, molecular modeling and QSAR results highlighted the suitability of PVP-CaCO3 blend for potential application as a biomaterial, such as bone-remineralization membrane.