Parkinson's disease is a neurodegenerative disorder that affects the central nervous system and is mainly characterized by the loss of dopaminergic neurons and pro‐oxidant mechanisms. Eugenol has been widely studied due to its anti‐inflammatory and antioxidant activities, making it a promising neuroprotective agent. This study aimed to investigate the effects of eugenol and its combined action with levodopa in the 6‐hydroxydopamine‐induced Parkinson's disease model. Wistar rats were subjected to intrastriatal injection of 6‐hydroxydopamine (21 μg) and then treated with eugenol (0.1, 1, or 10 mg/kg), levodopa (25 mg/kg) or their combination (eugenol 10 mg/kg + levodopa 12.5 mg/kg) orally for 14 days. On the 14th day, the animals were subjected to behavioural tests, and after euthanization and dissection of the brain areas, neurochemical analyses were performed. The results showed that eugenol reduced the oxidative stress and behavioural disturbances induced by 6‐hydroxydopamine. The eugenol and levodopa combination was more effective in some behavioural parameters and body‐weight gain in addition to promoting an increase in reduced glutathione levels compared to levodopa alone. Thus, the neuroprotective activity of eugenol was observed against motor and neurochemical disorders. Additionally, the eugenol and levodopa combination was promising when compared to conventional treatment.

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