Neurodegenerative diseases (NDDs) are a series of disorders characterized by the progressive loss of specific neurons, leading to cognitive and locomotor impairment. NDDs affect millions of patients worldwide but lack effective treatments. Dysregulation of lipids, particularly the accumulation of lipid droplets (LDs), is strongly implicated in the pathogenesis of NDDs. How LDs contribute to the occurrence and development of NDDs, and their potential as therapeutic targets remain to be addressed. In present review, we first introduce the processes of LDs formation, transportation and degradation. We then highlight how the accumulation of LDs contributes to the pathogenesis of NDDs in a cell type-specific manner. Moreover, we discuss currently available methods for detecting LDs and elaborate on LDs-based therapeutic strategies for NDDs. Lastly, we identify gaps that need to be filled to better leverage LD-based theranostics in NDDs and other diseases. We hope this review could shed light on the role of LDs in NDDs and facilitate the development of novel therapeutic strategies for NDDs.