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There is continued interest in the assessment and potential use of antioxidants as neuroprotective agents in diseases associated with increased oxidative stress, such as Parkinson's disease. The neuroprotective effect of a natural antioxidant drink, EM-X (a ferment derivative of unpolished rice, papaya and seaweeds with effective microorganisms), was investigated using the 6-hydroxydopamine (6-OHDA)-lesion rat model of Parkinson's disease. The nigrostriatal dopaminergic neurons were unilaterally lesioned with 6-OHDA (8 μg) in rats that were treated with a 10-times diluted EM-X drink (dilEM-X), standard EM-X drink (stdEM-X) or tap water for 4 days. Seven days post lesion, the integrity (no. of tyrosine hydroxylase positive cells (TH+ cells) in the substantia nigra pars compacta (SNpc)) and functionality (dopamine and its metabolites DOPAC and HVA content in the striata) of nigrostriatal dopaminergic neurons were assessed. In the vehicle-treated rats, infusion of 8 μg of 6-OHDA significantly reduced the number of TH+ cells in the SNpc as well as the levels of dopamine, DOPAC and HVA in the striata on the lesion side. The loss of TH+ cells, dopamine and HVA, but not the DOPAC levels, was significantly attenuated by stdEM-X pretreatment, but not by the dilEM-X pretreatment. There were no significant changes in the TH+ cells, or in the monoamine levels with the EM-X pretreatment per se, except for a small but significant fall in the levels of dopamine with the stdEM-X. The evidence presented supports the potential neuroprotective effects of stdEM-X drink, although its effect on dopamine levels needs further investigation.