Parkinson’s disease (PD) is one of the most common progressive neurodegenerative disorders and is characterized by behavioral dysfunction and the selective loss of dopaminergic neurons in the substantia nigra. DJ-1, a causative gene product of a familial form of PD, PARK7, has multiple functions; i.e., oxidative stress sensor, fertility, molecular chaperone and transcriptional regulation.  However, the relationship between DJ-1 and the onset of PD is not fully understood. This review describes current findings regarding the function of DJ-1 against oxidative stress-mediated disorders, such as PD and brain ischemia. In particular, we focus on the modification of DJ-1 protein, the distribution of DJ-1 protein in the brain, and the neuroprotective effects of DJ-1 protein. These findings suggest that DJ-1 may be an important therapeutic target in PD and for cytoprotective therapy in various oxidative-stress-mediated disorders.