Graphene nanomaterials have been the focus of tremendous attention not only in the field of basic research but also in technological applications, owing to their unique physicochemical dimensions such as good sensing ability, and excellent mechanical, thermal and electrical properties. On the other hand, ZnO nanomaterials have attracted considerable interest in relation to sensors due to their many advantages, including large surface-to-volume ratio, excellent biological compatibility, high electron-transfer rates, non-toxicity and biosafety. The development of biosensors can potentially be an interesting application for the utilization of these nanomaterials tremendously large surface-area-to-volume ratio, which is a dominating and promising parameter with the potential to solve biocompatibility and biofouling problems. The present chapter describes recent examples in the development of miniaturized amperometric and potentiometric biosensors by integrating enzymes and one of these two nanomaterials. The latest advances relating to the application of these biosensors to rapidly detect biomedically relevant substrates such as glucose, urea, uric acid, cholesterol, etc., with enormous prospects in clinical medicine applications are reviewed throughout. The presented biosensors exhibit good reproducibility, reusability, selectivity, rapid response times, long shelf life and high sensitivity, and do not suff er from interference by coexisting oxidable substances. These electrochemical nanobiosensors prepared through the integration of biomolecules with graphene or ZnO nanostructures have demonstrated that, besides enhancing the biosensing capabilities compared with conventional platforms, bring out new approaches such as miniaturization, reagentless biosensing and single-molecule detection. This chapter highlights the significant milestones achieved and further elucidates the emerging future prospects in this area.