BACKGROUND: Betaine has been shown to be antioxidantand methyl donor effects in our recent studies. OBJECTIVES: Inthe present study, the antioxidant and methyl donor properties ofbetaine in levodopa/benserazide-mediated hyperhomocysteinemiaand levodopa-induced oxidative stress in rat's kidney wereexamined. METHODS: Sprague-Dawley male rats were dividedinto levodopa (LD), Betaine (Bet.), levodopa plus betaine(LD/Bet.), levodopa plus benserazide (LD/Ben.), levodopa plusbetaine-benserazide (LD/Bet.-Ben.), and control groups. Theexperimental groups received LD (3 × 100 mg/kg), Bet. (1.5%w/w of the total diet), Ben. (3 × 25 mg/kg), and distilled waterwas given to controls for 10 consecutive days, orally by gavage.RESULTS: Plasma total homocysteine (tHcy) concentrationdecreased significantly in Bet.-, LD/Bet.-, and LD/Bet.-Ben.-treated rats compared to LD/Ben. group. Thiobarbituric acidreactive substances concentration (as a lipid peroxidationmarker) in renal tissue reduced statistically in betaine group incomparison with LD and LD/Ben. groups. Renal catalaseactivity increased significantly in LD-treated rats whencompared to controls. Renal superoxide dismutase activitysignificantly decreased in LD-treated group when compared toLD/Ben. group. However, there was not any significantdifference in renal glutathione peroxidase (GPx) activity amongthe groups. CONCLUSIONS: These findings indicate that LD andLD/Ben. have side effects in kidney due to induction ofhyperhomocysteinemia and oxidative stress. In contrast, betaineacts as a promising antioxidant and methyl donor agent versusLD-induced complications.