Cell-free DNA (cf-DNA), as extracellular nucleic acid fragments present in various human biofluids, 5 including the sources of cf-DNA, its inflammatory pathways, and the association between cf-DNA-induced inflammation and neurodegenerative diseases, are summarized in this reviw. We have also traced the characteristic changes of cf-DNA in neuroinflammation-related diseases such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis, and analyzed the latest applications of cf-DNA in early diagnosis of diseases, monitoring of courses of disease, and evaluation of therapeutic efficacy. This review is expected to provide references for related research.