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Conventional mitochondrial transplantation has been explored as a therapeutic strategy, but its emphasis on increasing mitochondrial quantity without restoring function has limited success. Recent advances in nanoengineered mitochondria that integrate isolated mitochondria with functional nanomaterials, offer new opportunities to enhance organelle quality, boost metabolic activity, and achieve targeted delivery. Preclinical studies highlight their promise in cardiovascular, neurodegenerative, and other age-related disorders. In this mini-review, mitochondrial dysfunction in aging is first introduced, followed by the summary of rational designed strategies for engineering mitochondrial biohybrids and their emerging applications, and finally translational challenges are further discussed. 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