Parkinson's disease (PD) is the second most common neurodegenerative disease in the world, severely affecting the quality of life of patients. Recent studies have shown that white matter (WM) plays a vital role in higher neurological functions such as behavior and cognition. In PD patients, neurodegeneration occurs not only in neuronal soma, but also in WM fiber bundles, which are composed of neural axons. The clinical symptoms of PD patients are related not only to the degeneration of neuronal soma, but also to the degeneration of WM. Most previous studies have focused on neuronal soma in substantia nigra (SN), while WM injury (WMI) in PD has been less studied. Moreover, most previous studies have focused on intracerebral lesions in PD, while less attention has been paid to the spinal cord distal to the brain. The above-mentioned factors may be one of the reasons for the poor treatment of previous drug outcomes. Neuroinflammation has been shown to exert a significant effect on the pathological process of brain and spinal cord neurodegeneration in PD. The NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome has been shown to activate and mediate neuroinflammation and exacerbate neurodegeneration in PD. NLRP3 inflammasome inhibition may be a potential strategy for the treatment of WMI in PD. This review summarizes recent advances and future directions regarding neuroinflammation-mediated WMI in PD and potential therapeutic strategies for targeting NLRP3 inflammasome in the brain and spinal cord, providing new insights for researchers to develop more effective therapeutic approaches for PD patients.