Nano-hydrogels or nanogels are a novel class of materials with various applications. Major breakthroughs in biosensor development have received widespread attention due to the incorporation of nanogels on electrodes. Nanogels can be used as the interfacing material for integrating inorganic-electrode materials with biorecognition elements such as antibodies, enzymes, and DNA. In applications requiring continuous sensing of biochemical parameters in complex environments such as blood, interstitial fluids, bioreactor fluids, the nanogels create protective layers by encapsulating bioreceptors, controlling the diffusion process and enhancing biocompatibility of sensing devices. The three-dimensional nano-network of the hydrogel preserves the activity of the biomolecules by providing an extracellular matrix-like microenvironment. Molecularly tailored nanogel particles enhances the surface area availability for enzyme loading and interaction with the substrate. The stability of enzymes in the nanogel membranes can be tuned by selecting an appropriate microenvironment using nano-hydrogels. In recent years, it has become routine for highly stable biosensors to use nano-hydrogels to entrap enzymes on microelectrodes. Additionally, recent studies demonstrate that nanogels can be used as effective platforms for designing wearable electronic devices for monitoring wound healing, pH, temperatures, seizures, electrocardiography (ECG) and sleep activity. Due to flexibility and tunable properties, "system-on-chip" devices can be created using the nanogels. This chapter will highlight the recent developments and potential application of nanogels in biosensor devices for environmental, clinical and health monitoring.