Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide, with an increasing incidence over the years. Its pathology is characterized by the abnormal aggregation of α-synuclein (α-Syn). The endoplasmic reticulum plays a critical role in maintaining protein homeostasis, and numerous studies have shown its involvement in the progression of PD and other neurodegenerative diseases. Under pathological conditions, various unfolded or misfolded proteins, including α-Syn, may cause endoplasmic reticulum stress (ERS) and interfere with normal cellular function. However, the molecular mechanism of ERS induced by α-Syn has not been fully elucidated. The article aims to summarize the correlation of α-Syn and ERS with the progression of PD, as well as the current progress in therapeutic research, thus providing new insights for the diagnosis and treatment of PD.