Piezo1 is a ubiquitously expressed non-selective cation channel protein found across various species. It possesses the ability to detect and respond to external mechanical forces, converting mechanical cues into intracellular bioelectrical events, thereby facilitating the propagation of electrochemical signals. Within the nervous system, Piezo1 is integral to synaptogenesis and myelination, modulation of pro-inflammatory mediators, neuropathic pain, cognitive processes, angiogenesis, and the regulation of cerebral hemodynamics, consequently impacting the pathogenesis and progression of neurological disorders. This review meticulously summarizes and synthesizes existing literature to provide an exhaustive overview of Piezo1's roles and mechanisms in a spectrum of neurological diseases, including neurodegenerative disorders, cerebrovascular accidents, traumatic brain injuries, gliomas, multiple sclerosis, and epilepsy. Additionally, it explores the potential therapeutic applications of targeting Piezo1. The discussion also encompasses the current research limitations, the imperative need for future investigations, and prospective strategies. Our analysis indicates that Piezo1 is a susceptibility gene for neurological conditions, and its expression inhibition may confer therapeutic benefits. In summary, this comprehensive review offers novel insights into the involvement of Piezo1 in neurological diseases and establishes a theoretical groundwork for the future development of Piezo1-targeted therapeutic interventions.