Metal-organic frameworks (MOFs) are emergent materials in diverse prospective biomedical uses, owing to their inherent features such as adjustable pore dimension and volume, well-defined active sites, high surface area, and hybrid structures. The multifunctionality and unique chemical and biological characteristics of MOFs allow them as ideal platforms for sensing numerous emergent biomolecules with real-time monitoring towards the point-of-care applications. This review objects to deliver key insights on the topical developments of MOFs for biomedical applications. The rational design, preparation of stable MOF architectures, chemical and biological properties, biocompatibility, enzyme-mimicking materials, fabrication of biosensor platforms, and the exploration in diagnostic and therapeutic systems are compiled. The state-of-the-art, major challenges, and the imminent perspectives to improve the progressions convoluted outside the proof-of-concept, especially for biosensor platforms, imaging, and photodynamic therapy in biomedical research are also described. The present review may excite the interdisciplinary studies at the juncture of MOFs and biomedicine.