Parkinson's disease (PD) is a widespread neurodegenerative disorder that exerts a broad variety of detrimental effects on people's health. Accumulating evidence suggests that mitochondrial dysfunction, neuroinflammation, α-synuclein aggregation and autophagy dysfunction may all play a role in the development of PD. However, the molecular mechanisms behind these pathophysiological processes remain unknown. Currently, research in PD has focussed on high mobility group box 1 (HMGB1), and different laboratory approaches have shown promising outcomes to some level for blocking HMGB1. Given that HMGB1 regulates mitochondrial dysfunction, participates in neuroinflammation, and modulates autophagy and apoptosis, it is hypothesised that HMGB1 has significance in the onset of PD. In the current review, research targeting multiple roles of HMGB1 in PD pathology was integrated, and the issues that need future attention for targeted therapeutic approaches are mentioned.