A combination of electrochemical and spectroscopic studies allows for understanding and describing the processes that occur on a nano-modified commercial pure Ti by Cu nanoparticles (CuNPs) in the presence and absence of tryptophan (Trp). The electrochemical results confirmed that the deposition of a thin CuNPs layer on the Ti substrate improves the corrosion resistance of the substrate under simulated physiological conditions. The addition of Trp to the corrosive environment accelerated the degradation of the CuNPs coating likely via the formation of a Cu-Trp complex. The degradation of the coating led to the formation of nano-galvanic sites at the substrate/ CuNPs coating interface, which in turn had a detrimental effect on the substrate and further increased the degradation of the coating. The conformational changes of Trp on the corroded CuNPs-Ti surface have been investigated by surface-enhanced vibrational techniques. Trp was adsorbed on the corroded CuNPs-Ti surface through the indole ring, which adopts a more/less horizontal orientation, and the protonated amine group in the presence of chloride and phosphate ions on the metallic surface. The application of a combination of infrared spectroscopy with atomic force microscopy (AFM-IR) proved that Trp covered the bimetal surface and caused the significant degradation of the surface.