The detection of blood glucose level receives much attention, because diabetes has become one of the significant threats to human health worldwide. In this paper, we described a novel core-shell MOF@MOF composite-based electrochemical sensor for nonenzymatic glucose sensing in alkaline media. The core-shell UiO-67@Ni-MOF composites were synthesized by internal extended growth of shell Ni-MOF on the core UiO-67 under polyvinylpyrrolidone (PVP) regulation. In the sensor system, UiO-67 with large specific surface area and good conductivity was used to accelerate the rate of electron transfer of UiO-67@Ni-MOF. Ni-MOF served as an electrocatalytic material due to excellent electrochemical activity toward glucose oxidation. The morphology, structure, and electrochemical performance of UiO-67@Ni-MOF composites were characterized. To demonstrate the detection performance of the UiO-67@Ni-MOF composite-based sensor, it was successfully used for nonenzymatic glucose sensing. The results indicated that UiO-67@Ni-MOF composites exhibited high electrocatalytic activity toward glucose oxidation compared with individual UiO-67 and Ni-MOF. Moreover, the sensor possessed high sensitivity and selectivity for real-time amperometric detection of glucose. It performed glucose level detection in human serum samples with acceptable reliability and accuracy. The present work suggested that the as-fabricated sensor is promising for nonenzymatic glucose sensing in real samples and holds great potential as an alternative tool for the rapid diagnosis of diabetes and for monitoring blood glucose levels daily. Display omitted •A novel core-shell MOF@MOF composite were synthesized by internal extended growth of shell Ni-MOF on the core UiO-67.•The UiO-67@Ni-MOF composites-based electrochemical sensor was presented for nonenzymatic glucose sensing.•The electrochemical sensor exhibited high selectivity and sensitivity for the detection of glucose in human serum.