At present, SCI lacks effective therapies, with mitochondrial dysfunction playing a central role in neuronal damage. Mitochondrial transplantation holds promise for restoring bioenergetic function. However, key challenges remain, including optimizing delivery methods, determining appropriate dosages, scalability, donor mitochondrial sourcing, regulatory hurdles and ensuring successful integration. Addressing these issues requires non-invasive platforms, validation in large-animal models, and clinical trials. This approach may bridge mitochondrial biology with translational engineering, thereby advancing the development of regenerative therapies for SCI.