Background: Parkinson’s disease (PD) is a neurodegenerative disease characterized by intracellular α-synuclein (α-Syn) deposition. Alternation of the α-Syn expression level in plasma or erythrocytes may be used as a potential PD biomarker. However, no studies have compared their prognostic value directly with the same cohort. Methods: The levels of α-Syn in plasma and erythrocytes, obtained from 45 PD patients and 45 control subjects, were measured with enzyme-linked immunosorbent assay. Then, correlation and receiver operating characteristic curve (ROC) analysis were performed to characterize the predictive power of erythrocytic and plasma α-Syn. Results: Our results showed that α-Syn expression levels in both plasma and erythrocytes were significantly higher in PD patients than in control subjects (823.14 ± 257.79 vs. 297.10 ± 192.82 pg/mL, p < 0.0001 in plasma; 3,104.14 ± 143.03 vs. 2,944.82 ± 200.41 pg/mL, p < 0.001 in erythrocytes, respectively). The results of the ROC analysis suggested that plasma α-Syn exhibited better predictive power than erythrocytic α-Syn with a sensitivity of 80.0%, specificity of 97.7%, and a positive predictive value of 77.8%. The expression level of plasma α-Syn correlated well with the age of patients, H-Y stage, MoCA scale, and UPDRS motor scale. On the contrary, there was no correlation between erythrocytic α-Syn level and clinical parameters in this study. Conclusion: Our results suggest that plasma α-Syn could be a specific and sensitive potential diagnostic biomarker for PD.