In recent years, a variety of biosensors based on manganese dioxide (MnO 2 ) nanostructures were used for the detection of different biomolecules. Structural versatility and different oxidation states of Mn present in MnO 2 nanostructures significantly enhance their biosensing applications. In this review, we have mainly focused on different morphologies of MnO 2 nanostructures and their role in different types of biosensors. We are elaborately discussing the electrochemical and optical-based biosensors on different morphologies of MnO 2 and their sensing techniques with proposed mechanisms. In electrochemical biosensors, various electrodes are available but there is a need for cheap, flexible, portable, and nontoxic electrodes. Therefore, we have discussed the fabrication of MnO 2 nanostructures on the surfaces of different types of electrodes and their real-time applications. MnO 2 nanomaterials are used in various optical biosensors due to their excellent light absorption properties, and they act as strong quenching agents. MnO 2 nanomaterials are termed "alternative natural enzymes" due to their significant enzyme-like activity. The study of various morphology-dependent sensing properties of MnO 2 nanostructures provides an insight into the development of many electrochemical and optical biosensors. Recently, MnO 2 based biosensors have earned great popularity as an alternative method for fast and easy detection of many biomolecules with very low detection limits.