The blood serum antioxidant status and the blood plasma metabolomic profile have been analyzed in Parkinson's disease (PD) patients, both pharmacologically naive and taking levodopa (treatment duration 7.4±5.4 years) at low (< 300 mg/day) and high (> 300 mg/day) doses. High-dose levodopa therapy caused changes in both the antioxidant status and metabolome of patients. High-dose levodopa treatment also activated lipid peroxidation, manifested by an increase in the level of lipid hydroperoxides. High-resolution mass spectrometry revealed accumulation of levodopa and dopamine metabolic products in the metabolome, particularly the neurotoxic dopamine metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL), and associated changes in related metabolic pathways. Low-dose levodopa treatment did not cause significant changes in the antioxidant status and metabolome of patients, thus suggesting that maintaining a low-dose regimen as long as possible could potentially reduce neurotoxic metabolite accumulation and also maintain normal antioxidant functions in PD patients.