The new system which consists of the thiol derivative of dipyrromethene–Cu(II) complex created on the surface of a gold electrode was applied for the first time for oriented immobilization of selected His-tagged domains of a receptor for advanced glycation endproducts (RAGE). Cyclic voltammetry (CV), Osteryoung square-wave voltammetry (OSWV), electrochemical impedance spectroscopy (EIS) and atomic force microscopy (AFM) were used for characterization of the redox active sensing layer. The biosensor proposed was applied for determination of Aβ16–23′ peptide. In its presence, a decrease of the maximum Cu(II) redox current was observed. These values correlated linearly with the Aβ16–23′ concentration in the range 0.001–1.000 µM. The presence of diluted human plasma has no influence on the sensor responses.