Abstract: Axonal degeneration is an early pathological feature of neurodegenerative diseases. Sterile alpha and TIR motif containing 1 (SARM1) is a unique member of the Myd88 adapter family; its Toll/interleukin-1 receptor domain promotes the process of axonal degeneration through regulating the nicotinamide adenine dinucleotide activity. This article reviews the role of SARM1 in various neurodegenerative diseases, such as amyotrophic lateral sclerosis, Parkinson's disease, multiple sclerosis, and Alzheimer's disease, and their SARM1-targeted corresponding treatment strategies, to provide ideas for new intervention and treatment strategies.