In Parkinson’s disease (PD), blood-brain barrier (BBB) dysfunction is shifting from being viewed as a passive marker of damage to a key pathological driver and potential therapeutic target. Its disruption involves mechanisms such as abnormal α-synuclein transport, tight junction breakdown, inflammatory activation, and vascular remodeling, all of which significantly disturb the neural microenvironment. Imaging technologies are playing an increasingly pivotal role in unraveling these complex processes. Based on current clinical and experimental evidence, this review outlines the major mechanisms of BBB disruption in PD and focuses on recent advances in multiscale imaging techniques for BBB research. It covers super-resolution microscopy, two-photon imaging, MRI, and PET, emphasizing their critical value in mechanistic investigation, functional assessment, and target localization. Multimodal imaging enables cross-scale integration—from nanoscopic to macroscopic levels, and from laboratory research to clinical application—and holds promise for building a “mechanism–imaging–intervention” framework that may accelerate the translation from pathophysiological understanding to clinical intervention.

The blood-brain barrier (BBB) plays a crucial role in the onset and progression of neurodegenerative diseases, particularly in the pathophysiology of Parkinson’s disease (PD). Under normal physiological conditions, the BBB maintains the barrier function between the central nervous system (CNS) and the peripheral circulation, precisely regulating molecular transport to prevent the infiltration of pathogens and harmful substances into the brain. However, BBB disruption may lead to the accumulation of neurotoxic substances, ultimately resulting in irreversible neuronal damage. In PD, BBB impairment has been implicated as a contributing factor to α-synuclein (α-syn) aggregation, oxidative stress, and chronic neuroinflammation, collectively accelerating neurodegeneration. This review focuses on BBB alterations associated with PD, integrating multimodal imaging techniques and clinical studies to systematically analyze its pathological characteristics. By thoroughly examining BBB changes in PD patients, this study aims to identify potential therapeutic targets and provide novel insights for optimizing diagnostic and intervention strategies. A comprehensive understanding of the structural and functional changes of the BBB in PD will facilitate the development of more precise diagnostic approaches and innovative therapeutic strategies.