Herein, graphene nanosheets (GNs) modified glassy carbon electrodes (GCE) with sequentially electrodeposited manganese oxides (MnOx) and nickel oxides nanoparticles (NiOx NPs) were suggested as efficient and durable anodes for glucose oxidation reaction (GOR). The electrocatalytic activity of the various prepared electrodes towards GOR was evaluated by cyclic voltammetry (CV) and chronoamperometry. Furthermore, scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), mapping EDX and X-Ray diffraction (XRD) techniques were used to characterize the electrocatalysts. The embedding of these nanostructured metal oxides in the GNs significantly enhanced their activity and stability for GOR. Moreover, the amended GNs with a combination of the two metal oxides (i.e., MnOx and NiOx, where NiOx is the top layer) showed the best electrocatalytic activity and stability for GOR compared to the unmodified GCE or those modified with GNs together with a respective single oxide. These outstanding enhancements are attributed to a synergistic effect between the two metal oxides and GNs matrix, where MnOx is believed to enhance the glucose molecules adsorption and improve the NiOx NPs conductivity via increasing of the content of Ni3+ (NiOOH). Besides, GNs are believed to stabilize and increase the nickel oxyhydroxide (NiOOH) surface concentration. The proposed anode showed high selectivity towards GOR in the presence of several electroactive species with prolonged stability.