Core-shell carbon sphere (CS)@α-Fe2O3@Ag was synthesized via a multistep hydrothermal method. First, the D-glucose hydrothermal process was employed to synthesize micron-size CSs on which α-Fe2O3 was grown to obtain the composite sphere of CS@α-Fe2O3. Thereafter, Ag+ was reduced on the surface of the CS@-Fe2O3 sphere using NaBH4 agent to produce the core-shell CS@α-Fe2O3@Ag. Finally, microsphere composite CS@α-Fe2O3@Ag was coated on a glassy carbon electrode (GCE) to enhance its electrochemical performance in the simultaneous determination of uric acid (UA), xanthine (XN), and hypoxanthine (HP). Results indicated that the CS@α-Fe2O3@Ag-coated GCE exhibited improved voltammetric sensitivity toward UA, XN, and HP compared to bare GCE. The oxidation peak currents of the simultaneous detection of UA, XN, and HP increased linearly in the concentration range of 0.5-8.0 µmol L-1. The detection limits of the fabricated electrodes for UA, XN, and HP were ~0.042, 0.089, and 0.048 µmol L-1, respectively, being more sensitive than many other modified GCEs. Moreover, the CS@α-Fe2O3@Ag-coated GCE exhibited good stability and repeatability. This study opens a new perspective for developing highly efficient electrodes for electrochemical analysis.