<p>Gold nanoparticle-based colorimetric detection of Hepatitis C virus (HCV) holds significant promise as a potential gold standard assay for early diagnosis and prognosis. Despite notable advancements in this field, a critical limitation persists in stabilizing gold nanoparticles (Au NPs) for extended periods, hindering their application in point-of-care devices. While polymeric capping has been frequently employed to enhance Au NP stability, its impact on the performance of colorimetric detection assays remains underexplored. In this study, we have analyzed the effect of polymeric stabilizing agents, such as polyvinyl alcohol (PVA) and polyethylene glycol (PEG) on the colorimetric detection of HCV. Additionally, we have evaluated the feasibility of using commercially available Au NPs for the assay. The findings revealed that PVA and PEG significantly improve molecular stability and shelf life of Au NPs. However, the interaction between synthetic oligomers and Au NP surfaces, influenced by the polymeric chelators, altered the biochemical properties, leading to variations in the assay’s ability to distinguish between positive and negative HCV samples. This preliminary investigation highlights the dual impact of polymeric chelators in enhancing Au NP stability and influencing assay performance. Future optimization is required to fully leverage their potential in meeting the standards for reliable colorimetric detection.</p>