Advanced anodic SnO nanoporous structures decorated with CuO nanoparticles (NPs) were employed for creatinine detection. Anodization of electropolished Sn sheets in 0.3 M aqueous oxalic acid electrolyte under continuous stirring produced complete open top, crack-free, and smooth SnO nanoporous structures. Structural analyses confirm the high purity of rutile SnO with successful functionalization of CuO NPs. Morphological studies revealed the formation of self-organized and highly-ordered SnO nanopores, homogeneously decorated with CuO NPs. The average diameter of nanopores is ∼35 nm, while the average CuO particle size is ∼23 nm. Density functional theory results showed that SnO@CuO hybrid nanostructures are energetically favorable for creatinine detection. The hybrid nanostructure electrode exhibited an ultra-high sensitivity of around 24343 μA mM cm with an extremely lower detection limit of ∼0.0023 μM, a fast response time (less than 2 s), and wide linear detection ranges of 2.5-45 μM and 100 μM to 15 mM toward creatinine. This is ascribed to the creation of highly active surface sites as a result of CuO NP functionalization, SnO band gap diminution, and the formation of heterojunction and Cu(1)/Cu(ll)-creatinine complexes through secondary amines which occur in the creatinine structure. The real-time analysis of creatinine in blood serum by the fabricated electrode evinces the practicability and accuracy of the biosensor with reference to the commercially existing creatinine sensor. The proposed biosensor demonstrated excellent stability, reproducibility, and selectivity, which reflects that the SnO@CuO nanostructure is a promising candidate for the non-enzymatic detection of creatinine.