Objectives The aim of this study was to evaluate a possible relationship between DRD2/ANKK1 (rs1800497) and SLC6A3/DAT1 (rs28363170) gene polymorphisms with the response to levodopa (L‐DOPA)‐therapy in patients with Parkinson's disease (PD). Methods One hundred and ninety‐five patients with idiopathic PD were investigated. Patients were genotyped for rs1800497 and rs28363170 polymorphisms using PCR‐RFLP. Logistic regression was performed to assess the association of polymorphisms with the occurrence of the chronic complications of L‐DOPA therapy. Key findings Our results showed association between the occurrence of dyskinesia with an increased greater disease severity (P = 0.007), higher L‐DOPA dose (P = 0.007) and use of dopamine agonist (P = 0.020). Moreover, there were significant protective effects for age (P = 0.004) and male subjects (P = 0.006). Conclusions Clinical and demographic characteristics of Brazilian PD patients and differences in DRD2 and DAT1 genes may to determine individual variations in the therapeutic response to L‐DOPA in the Brazilian PD patients.