A strategy for the rational design of a novel colorimetric sensor based on dithioerythritol-modified gold nanoparticles for the selective recognition of Hg²⁺ in aqueous media is presented. This approach relies on the combination of gold nanoparticles with Hg²⁺ through sulfur−Hg²⁺−sulfur interaction. The gold nanoparticles showed high selectivity toward Hg²⁺ with binding-induced red shift in the absorption spectra, with no response to major interfering cations such as Pb²⁺, Cd²⁺, and Cu²⁺ in the presence of ethylenediamine tetraacetic acid. The system responds to Hg²⁺ with a detection limit of 100 nM and might open a new avenue for the development of Hg²⁺ sensing probes.