Nanostructures that can undergo redox reactions have significant potential for electrochemical analysis. They can act as signal amplifiers to determine concentrations of targets in biological samples. In this work, a rational combination of electroactive copper‐based metal‐organic frameworks (Cu‐MOFs) and ferrocene carboxylic acid (Fc) was designed for ratiometric electrochemical detection of creatinine. The synthesized Fc@Cu‐MOFs exhibited two redox signals from the Cu²⁺/Cu⁺ and Fe³⁺/Fe²⁺ systems in the skeleton of Cu‐MOFs and Fc, respectively. In the presence of chloride (Cl⁻), the oxidation current of Cu⁺ increased due to formation of solid‐state cuprous chloride (CuCl). Adding strong Cu⁺ chelators, e. g. creatinine, coordinated with Cu⁺ and caused the current output of solid‐state CuCl to decrease significantly. The anodic current of Fc did not appreciably change, serving as an internal reference signal. The ratiometric responses (I_Cu(I)/I_Fc) changed with increasing concentrations of creatinine from 0.017–130 μM with a detection limit (S/N=3) of 0.005 μM. The main advantages of Fc@Cu‐MOFs are the low LOD, high selectivity, and reliability, making it a suitable platform for determining creatinine in human serum and urine samples. The as‐fabricated sensor is a reliable approach for determining (bio) molecules that can form stable complexes with Cu⁺ ions.