The development of biocompatible and efficient nanoplatforms that combine diagnostic and therapeutic functions is of great importance for precise disease treatment. Melanin, an endogenous biopolymer present in living organisms, has attracted increasing attention as a versatile bioinspired functional platform owing to its unique physicochemical properties (e.g., high biocompatibility, strong chelation of metal ions, broadband light absorption, high drug binding properties) and inherent antioxidant, photoprotective, anti-inflammatory, and anti-tumor effects. In this review, the fundamental physicochemical properties and preparation methods of natural melanin and melanin-like nanoparticles were outlined. A systematical description of the recent progress of melanin and melanin-like nanoparticles in single, dual-, and tri-multimodal imaging-guided the visual administration and treatment of osteoarthritis, acute liver injury, acute kidney injury, acute lung injury, brain injury, periodontitis, iron overload, etc. Was then given. Finally, it concluded with a reasoned discussion of current challenges toward clinical translation and future striving directions. Therefore, this comprehensive review provides insight into the current status of melanin and melanin-like nanoparticles research and is expected to optimize the design of novel melanin-based therapeutic platforms and further clinical translation.