Parkinson’s disease (PD) is the second most common neurodegenerative disease after Alzheimer’s disease (AD). The pathologic hallmarks of the disease are the loss of dopaminergic neurons of substantia nigra pars compacta and the presence of intraneuronal alpha synuclein (a-syn) aggregates. Clinical features of PD include motor symptoms such as bradykinesia, rigidity, tremors, postural instability, and gait impairment, and non-motor symptoms such as constipation, orthostatic hypotension, REM sleep disorder, depression and dementia. Currently, there is no disease-modifying therapy for PD. Several human studies have shown that exercise reduces progression of motor symptoms, improves performance on cognitive tasks, and slows functional deterioration. However, regular exercise may not always be feasible in PD patients. Irisin is an exercise-induced myokine involved in metabolism modulation and body fat reduction, but it also crosses the blood-brain barrier and may mediate some of the benefits of exercise in brain function. Recent evidence has shown that irisin could be therapeutically promising in PD as an “exercise-mimicking” intervention. Exogenous irisin administration decreases brain a-syn pathology and loss of dopaminergic neurons, while it improves motor outcomes in preclinical models. Several other neurodegenerative disorders such as AD share common underlying pathogenetic mechanisms with PD such as protein misfolding and aggregation, neuroinflammation, brain metabolic abnormalities, and neuronal loss. Therefore, investigation of irisin as a disease-modifying therapy could be promising for PD and other neurodegenerative disorders including AD.