Herein, we present the development of a far-infrared spectroscopic approach for studying metalloenzyme active sites in a redox-dependent manner. An electrochemical cell with 5 mm path and based on silicon windows was found to be appropriate for the measurement of aqueous solutions down to 200 cm−1. The cell was probed with the infrared redox signature of the metal–ligand vibrations of different iron–sulfur proteins. Each FeS cluster type was found to show a specific spectral signature. As a common feature, a downshift of the frequency of the FeS vibrations was seen upon reduction, in line with the increase of the FeS bond. This downshift was found to be fully reversible. Electrochemically induced FTIR difference spectroscopy in the far infrared is now possible, opening new perspectives on the understanding of metalloproteins in function of the redox state.