Several possible configurations (CS/NI1-10) for the surface adsorption of 5-nitroisatin (NI) on the chitosan polymer (CS) were investigated using quantum mechanical methods in the gas and solution phases. The values of the binding energies indicate the energetic stability of these configurations. The solvation energies demonstrate that the solubility of NI and CS increases in the presence of each other. The role of hydrogen bonds in noncovalent surface functionalization was determined by AIM analysis. The mechanism of covalent surface functionalization and the explicit solvent effects (methanol) in this mechanism were investigated and it was determined that the covalent functionalization through Schiff base formation is possible. These findings, in addition to the biological applications of the chitosan Schiff bases and their complexes, led us to synthesize a new Schiff base from condensation reaction of CS and NI (CSB) together with its Ni(II) and Cu(II) complexes. The synthesized compounds were characterized by the elemental analysis, infrared spectroscopy (IR), thermogravimetry analysis (TGA) and differential scanning calorimetry (DSC). Also, optimized geometries, assignment of the IR vibrational bands as well as exploring of the frontier orbitals of the synthesized compounds have been calculated using density functional levels of theory.