Sulfur containing amino acids play an important role in human physiology, and different levels of amino acids in organisms can cause serious health problems. Herein, we have developed a core-shell Cu@Au nanoparticles (Cu@AuNPs)-based powerful colorimetric sensing array for differentiation of containing amino acid. The sensors consist of two different concentrations of iodides (1.5 μM KI and 0.5 μM NaI) as sensor receptors and Cu@AuNPs as signal readout. With the amino acids, iodide can easily get access to the Cu@AuNP surface, inducing a visual color variation (gray→red) of the Cu@AuNP solution by means of changing the Cu@AuNP clusters to separated, spherical-like, and larger ones. While without the target amino acids, various amino acids show differential binding interactions toward Cu@AuNPs via gold-sulfur bonds. So, the transformation is blocked to diverse degrees due to a competition adsorption between amino acids and iodides to the Cu@AuNPs. Consequently, varying levels of Cu@AuNP transformation are relevant with different amino acids and iodides, generating distinct colorimetric reaction modes, which are characteristic for each amino acid and can be quantitatively detected by linear discriminant analysis (LDA). Four target amino acids have been successfully identified at the 20 nM level. Additionally, the sensing system shows outstanding potential for analysis of complex samples.