Neurodegenerative diseases are a group of disorders characterized by chronic progressive degeneration of neurons in the brain and/or spinal cord. Their etiology remains unclear and the pathogenesis is complex. To date, there are no effective treatments. In recent years, the roles of mitochondria-localized silent information regulator（SIRT）family members, including SIRT3, SIRT4, and SIRT5, in neurodegenerative diseases have attracted increasing attention. Accumulating evidence demonstrates their involvement in critical processes of neuronal degeneration by regulating mitochondrial function, inflammatory responses, and so on. This review summarizes the research advances on mitochondrial SIRTs in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS), aiming to provide new insights for elucidating disease pathogenesis and developing prevention/therapeutic strategies.