BACKGROUND: Exercise is a widely recognized non-pharmacological treatment for Parkinson's Disease (PD). The bidirectional regulation between the brain and peripheral organs has emerged as a promising area of research, with the mechanisms by which exercise impacts PD closely linked to the interplay between peripheral signals and the central nervous system. AIM OF REVIEW: This review aims to summarize the mechanisms by which exercise influences peripheral-central crosstalk to improve PD, discuss the molecular processes mediating these interactions, elucidate the pathways through which exercise may modulate PD pathophysiology, and identify directions for future research. KEY SCIENTIFIC CONCEPTS OF REVIEW: This review examines how exercise-induced cytokine release promotes neuroprotection in PD. It discusses how exercise can stimulate cytokine secretion through various pathways, including the gut-brain, muscle-brain, liver-brain, adipose-brain, and bone-brain axes, thereby alleviating PD symptoms. Additionally, the potential contributions of the heart-brain, lung-brain, and spleen-brain axes, as well as multi-axis crosstalk-such as the brain-gut-muscle and brain-gut-bone axes-are explored in the context of exercise therapy. The study highlights the need for further research into peripheral-central crosstalk and outlines future directions to address challenges in clinical PD therapy.