In this study, the synthesis of Cu-MOF-199@multiwalled carbon nanotubes (Cu-MOF-199@MWCNTs) composites was achieved and utilized to create an advanced electrochemical sensor for creatinine (Cre) detection. The composites were modified on a glassy carbon electrode surface through direct drip coating, followed by the deposition of copper nanoparticles (CuNPs) via constant potential deposition. Characterized by various techniques and electrochemical analyses, the Cu-MOF-199@MWCNTs composite increased the CuNPs load, improving the detection sensitivity for Cre. Under optimal conditions, the modified electrode exhibited good linearity across a broad range of Cre concentrations (0.05-40.0 μM) with a low detection limit of 11.3 nM. The developed sensor demonstrated remarkable stability, reproducibility, and selectivity, showing promise in sensitive and accurate Cre detection in serum samples.