An investigation of the electrostatic interactions between histidine and silver have been analyzed using density functional theory (DFT). Variations in the structural parameters were identified to be significant at those atoms of histidine near the silver cluster. The shifting of frontier molecular orbitals, reduction in bandgap, molecular electrostatic potential (MEP), and overlap of natural bond orbitals (NBO) between silver and histidine have been theoretically calculated. The results confirm the redistribution of charges consequent to the process of adsorption. On the basis of time-dependent density functional theory (TDDFT), two peaks were generated at 301 and 409 nm in the simulated UV-vis spectrum. Theoretical vibrational Raman analysis of the investigated molecules strongly confirms the process of adsorption. Nonlinear optical (NLO) properties are predicted by theoretical studies and confirmed experimentally via open-aperture Z-scan. The adsorption of histidine on silver enhances the NLO parameters, indicating that it is a promising candidate for NLO devices.