Degradation of thiolate self-assembled monolayers (SAMs) in ambient conditions and liquid environments seriously limits the fabrication of thiol-based devices. Here, we demonstrate that nanostructured gold exhibits higher resistance to SAM degradation and increased electrochemical stability against thiolate desorption in relation to polycrystalline preferred oriented Au(111). The increased stability can be related to the presence of a large number of defects, such as adatoms, vacancies, and steps where the thiolate binding energy is stronger than at terraces. The nanostructured Au is an interesting platform because it can be easily prepared, has surface enhanced Raman spectroscopy (SERS) activity, and exhibits a high signal/noise ratio for amperometric detection because of its large real surface area.