Purpose In this study, the effects of glutathione S-transferase polymorphisms Mu1 (GSTM1) and glutathione S-transferase polymorphisms Theta1 (GSTT1 ) on Parkinson's disease (PD) risk factor were evaluated in a Tunisian population. Methods These polymorphisms were analyzed in 229 healthy Tunisian subjects and 64 Tunisian patients with PD, using a polymerase chain reaction (PCR). Statistical analysis was performed using SPSS 18.0. The relative associations between the GST genotypes and PD were assessed by calculating the odds ratios (ORs) and 95% confidence intervals (CIs). Results The study results demonstrated that the individuals with GSTM1 [OR = 3.93, 95% CI: 1.98–7.92, P = 10−6] and GSTT1 [OR = 5.45, 95% CI: 2.90–10.30, p = 10−6] were statistically associated with the risk of PD. A significant association was also found between the individuals with both GSTM1/T1 null genotypes and PD risk [OR = 22.10, 95% CI: 6.99–73.75, P = 10−6]. Conclusion These genotyping findings suggest that the absence of both GSTM1 and GSTT1 activity could be a contributory factor for the development of PD.