A simple, sensitive and efficient colorimetric assay platformfor the determination of Cu2+ was proposedwith the aimof developing sensitive detection based on the aggregation of AuNPs in presence of a histamine H2-receptor antagonist (famotidine, FAM) as recognition site. This study is the first to demonstrate that themolar extinction coefficients of the complexes formed by FAMand Cu2+ are very low(by analyzing the chemometricsmethods on the first order data arising from different metal to ligand ratio method), leading to the undesirable sensitivity of FAM-based assays. To resolve the problemof lowsensitivity, the colorimetry method based on the Cu2+-induced aggregation of AuNPs functionalized with FAMwas introduced. This procedure is accompanied by a color change from bright red to blue which can be observed with the naked eyes. Detection sensitivity obtained by the developed method increased about 100 fold compared with the spectrophotometry method. This sensor exhibited a good linear relation between the absorbance ratios at 670 to 520 nm (A670/520) and the concentration in the range 2–110 nMwith LOD=0.76 nM. The satisfactory analytical performance of the proposed sensor facilitates the development of simple and affordable UV–Vis chemosensors for environmental applications.