Abstract Hydrogen gas exhibits broad therapeutic potential in the biomedical field. However, low solubility and the lack of targeted delivery limit its clinical application. Nanotechnology offers a solution with externally stimulated responsive nanomaterials capable of controlled hydrogen production under stimuli such as light, ultrasound, magnetic fields, and microenvironments, overcoming traditional delivery limitations. This review systematically summarizes the mechanisms of action of such materials, covering hydrogen evolution mechanisms such as semiconductor catalysis and coordination of chemistry‐driven processes, and explores their biomedical applications in cancer therapy, the treatment of inflammatory diseases, organelle and neurovascular protection, antimicrobial therapy, and imaging‐guided synergistic treatment. Finally, this review analyzes key challenges, including material biocompatibility and regulation of hydrogen concentration thresholds, and looks ahead to the optimization of material design through multidisciplinary collaboration, the establishment of safety evaluation standards, and the advancement of nanohydrogen medicine from basic research to precise clinical application.