Background/Objectives: Parkinson’s disease (PD) is a neurodegenerative disease with a heterogeneous nature. Many molecular pathways are engaged in PD pathogenesis. Granzyme B (GrB) is an enzyme released by CTLs and has roles in neuroinflammation, axonal degeneration, demyelination, and neuronal ischemic death. However, little is reported about its role in PD pathogenesis and deterioration. To evaluate the role of GrB in PD. Method: A total of 94 participants were recruited from outpatient neurology clinics (47 PD patients and 47 healthy controls). Serum GrB levels were measured using ELISA. Results: Among PD patients, the age of onset was 57.30 ± 4.92 years, and the duration of illness was 7.13 ± 4.20 years. Sociodemographic data revealed statistically significant associations between the development of PD and HCV infection (0.001*), family history of neuropsychiatric illness (0.004*), and/or PD (0.028*). MoCA TS showed a significant reduction in cognitive performance among PD patients even after correction (p < 0.001*). H_Y score showed that >50% of PD patients were clustered in stages 1 and 2, and motor scores showed a substantial reduction. GrB levels were markedly increased among PD patients compared with the control group (1721.4 ± 588.8 pg/mL vs. 418.4 ± 131.3 pg/mL) (p < 0.001*). This indicates a strong association between elevated granzyme B and PD. However, no statistically significant correlations were observed between GrB levels and the parameters studied. Conclusion: GrB levels are significantly elevated among PD patients. This reflects underlying immune activation or inflammatory processes associated with the progression of PD. GrB showed a promising diagnostic association with PD, but was not correlated with disease severity, activity, or duration in this cohort. Formal evaluation of GrB’s diagnostic accuracy in an independent, disease-control-inclusive cohort is warranted before it can be considered a diagnostic biomarker.