The word biomimetics is comparatively recent in the area of biosensors, while being used for many years by biochemists. Biomimetics often aims to intelligently employ natural or synthetic materials without using live systems. Drug administration and sensing techniques are only two of the many uses for macromolecules that mimic biodegradation or their mixtures, a significant category of biomimetics. Biomimetic macromolecule-based detection methods are the interesting ways to get around the problems with biosensors and make them better at finding biological targets, especially signs of tumours. The area of biosensors based on biomimetic macromolecules has seen a number of noteworthy advancements in recent years. With an emphasis on sensing techniques based on mimetic biodegradable macromolecules and their composites, the present chapter provides an overview of these advancements. The merit indices of biosensors, including biocompatibility, biodegradability, antifouling, sensitivity, selectivity, etc., may be enhanced by using the unique properties of biodegradable macromolecule-based composites that can replicate biological systems. Furthermore, these composites provide a chance for in-situ continuous monitoring biomarkers and real-time biomarkers. In this chapter, I have attempted to demonstrate the great potential of these biomacromolecules (natural or synthetic) and their composites in implantable or wearable sensing systems and other customized sensors. Lastly, a summary of the field’s existing issues and prospects for growth was provided.