Molecular self-assembly has become a popular tool to prepare nanomaterials with potential applications, such as ion-responsive detection of Hg²⁺ in aqueous solutions. In this study, FFACD aromatic pentapeptides, whose N-terminuses were protected by carboxyl (Ac-FFACD) or a 9-fluorenylmethoxycarbonyl group (Fmoc-FFACD), were chosen as building blocks to produce nanostructures in solutions. Based on the preliminary determination of the critical aggregation concentration (CAC) of Ac-FFACD and Fmoc-FFACD aromatic pentapeptides in water, the order of magnitude of which is 10^–5 mol·L^–1, self-assembled spiral and networked nanowires can be easily obtained over a range of concentrations. These nanowires were characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), and atomic force microscopy (AFM). The self-assembled spiral and networked nanowires were designed to be used as templates for preparing CdS quantum dots (QDs) in-situ at room temperature. The peptide-functionalized, nanowire-encapsulated CdS QDs can be used for rapid, sensitive, and selective detection of trace amounts of mercuric ions (Hg²⁺) in aqueous solutions. This method enables rapid, linear detection (the linear correlation coefficients are 0.9972 of ΔF = 257.09 + 3.58 c_Hg²⁺ for Ac-FFACD and 0.9994 of ΔF = 48.13 + 32.96 c_Hg²⁺ for Fmoc-FFACD) with the Hg²⁺ limit of detection at 300.85 ng·L^–1 and 32.09 ng·L^–1 for Ac-FFACD and Fmoc-FFACD, respectively. The supramolecular, self-assembled nanowires, fabricated from the two aromatic pentapeptides and having encapsulated QDs, exhibit superior properties attributable to the large loading capacity and the coordination sites of these peptides with Hg²⁺. These structures can serve as novel Hg²⁺ sensors and have possible applications for detection of various targets in scientific and engineering systems.