The functionalization of the nanoparticle’s (NP) surface is one method for tuning their overall properties to fit targeted applications. We developed a nanosensor based on the specific supramolecular interactions between ß-cyclodextrin (ßCD) nanocavities and organic molecules of biological interests using the metal-enhanced fluorescence effect (MEF) as the detection signal. We grafted ßCD, a typical macrocyclic host molecule that interacts specifically with different organic molecules and changes their physical properties (such as their fluorescence emission intensity), on gold NPs. To evaluate this nanosensor and the effect of the metallic core, we worked with a typical organic molecule, Rhodamine B (RhB), that has a strong association constant with ßCD (5700 M − 1) and is well-known to be quenched in the presence of cyclodextrins (CDs). The results show that, by grafting ßCD on gold NPs, it is possible to increase the sensitivity of RhB detection by 70%, 80%, and 294% when compared with solutions in (1) a phosphate buffer, (2) with ßCD, and (3) with Au NPs, respectively. These results show that the use of a supramolecular system attached to a metallic NP can interact specifically with a dye to enhance its fluorescence emission through the MEF effect. Moreover, this type of nanosystem can overcome the quenching of the signal by the matrix, such in the case of RhB with CDs. Eventually, this concept could be extended to other dyes with different quenching effects. For this reason, this type of nanosensor system could be used in the future to protect and enhance the dye emission of fluorophores in different biological media.