The core-shell structured nanomaterial of MgCo2O4@MnO2 on nickel foam (MCMNA/NF) was synthesized via a two-step hydrothermal method. It can be used as a self-supported electrode, which was constructed to an electrochemical sensor for sensitive measurement of glucose. The core-shell structure with a MnO2 shell significantly enhances the material’s specific surface area and accelerates the electron transport process. Electrochemical catalytic oxidation tests were conducted on core-shell structured MCMNA/NF nanocomposite as a working electrode. The sensitivity is determined to be 9.37 μA·mM−1·cm−2 and the detection limit is 0.02 mM. These test results demonstrate that the material exhibits excellent stability and selectivity as a glucose sensor. The synergistic effect of MgCo2O4 and MnO2 can effectively promote the application performance of the electrode materials. The MgCo2O4@MnO2 glucose sensor material also exhibits exceptional resistance to interference, demonstrating no interference from Urea, Citric acid (CA), Ascorbic acid (AA), or specific inorganic salts during blood glucose detection.