The aim of the present paper is to highlight a novel electrochemical assay for an extremely-selective detection of fructose thanks to the use of a supramolecular complex between beta-cyclodextrins (beta-CDs) and a chemically modified ferrocene with boronic acid named 4-Fc-PB/natural-beta-CDs. Another kind of beta-CDs, the 4-Fc-PB/3-phenylboronic-beta-CDs, is proposed for the detection of glucose. The novel electrochemical probe is fully characterized by H-1 nuclear magnetic resonance, mass spectroscopy, and elemental analysis, while the superior electrochemical performance is assessed in terms of sensitivity and detection limit. The novelty of the present work consists in the role of CDs that for the first time are employed in electrochemistry with a unique detection mechanism based on specific chemical interactions with the target molecule by the introduction of proper binding groups. A highly selective detection of fructose is obtained and it is believed that the proposed mechanism of detection represents a new way to electrochemically sense other molecules by varying the combination of specific groups of the supramolecular complex. The findings are of impactful importance since a quick, easy, cheap, and extremely selective detection of fructose is not yet available in the market, here achieved by using electrochemical methods which are a very growing field.