Evidence for interactions between π-electron-rich calixarene cavities and the surface of gold nanoparticles is demonstrated using a comparative synthetic approach involving the capping of the nanoparticles with thiol ligands. In one approach, thiol ligands are systematically titrated onto existing 5.3 nm gold nanoparticles in solution (postsynthetic synthesis approach), whereas in the other a gold solution is reduced in the presence of thiol ligands (direct synthesis approach). The calixarene cavity is placed in close proximity and facing toward the gold nanoparticle surface upon adsorption of ligand 5,11,17,23-tetrakis-mercaptomethyl-25,26,27,28-tetrapropoxylcalix[4]arene (MMC), which comprises four upper-rim thiol groups. The other two ligands used in this investigation contain either four thiol groups on the calixarene lower-rim, 25,26,27,28-tetrakis(4-mercaptobutyloxy)calix[4]arene (MBC), or a model monodentate thiol, 4-methoxybenzenemethanethiol (MBM), as controls. The orientation of the cavity in MMC is toward the gold surface upon adsorption, which is in complete contrast to its isomer MBC in which the cavity points away from the surface and is located further away. Control ligand MBM lacks a calixarene cavity though still possessing an electron-rich arene ring in close proximity to the gold nanoparticle surface upon adsorption. The surface plasmon resonance absorption (SPR) band red shifts 5 nm in wavelength and increases 10% in absorption intensity during titration of the gold surface with MMC, as monitored via UV−vis spectroscopy, until the onset of surface site saturation, which corresponds to a molecular footprint of 116 Å2 per MMC molecule. Using MBC under identical conditions produces no change in either the SPR band wavelength or absorbance. Adsorption of ligand MBM to the gold nanoparticle surface results in a similar increase as MMC on the SPR absorption intensity and no change in SPR band wavelength. These results can be understood on the basis of interactions between the π-electron-rich calixarene cavity and metal surface. The influence of the calixarene cavity on SPR band wavelength was also observed in nanoparticles prepared by the direct synthesis approach, in which gold reduction occurred in the presence of thiol ligand. The MMC-capped nanoparticles had a higher SPR band wavelength relative to those capped with MBC and MBM. Altogether, these results demonstrate that even for colloids that are relatively large compared with molecular clusters, subtle characteristics of the capping ligand such as the presence of a π-electron rich cavity influence surface microenvironment upon adsorption.