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Current pharmacological approaches have failed to provide complete remission for patients with Attention-Deficit/Hyperactivity Disorder (ADHD). This study aimed to evaluate the efficacy and tolerability of resveratrol (that have been shown to have antioxidative, anti-inflammatory, and anti-apoptotic effects) as an adjunct to methylphenidate in pharmacologic treatment of ADHD. This 8-week, double-blinded, placebo-controlled trial randomized 66 participants to receive either 500 mg/day resveratrol or matched placebo in addition to methylphenidate. ADHD symptoms were evaluated in the patients using the Parent and Teacher versions of ADHD-Rating Scale (ADHD-RS) at three measurement points with time intervals of 4 weeks. Furthermore, the tolerability of the treatment strategies was systematically compared. Repeated measures analysis demonstrated a significant effect for time–treatment interaction on all three subscales of the Parent ADHD-RS during the trial period (total: p = 0.015; inattention: p = 0.032; hyperactivity/impulsivity: p = 0.036). Nevertheless, the effect for time–treatment interaction was not significant for the Teacher version of ADHD-RS (total: F = 0.81, df = 1.33, p = 0.401; inattention: F = 0.57, df = 1.37, p = 0.507; hyperactivity/impulsivity: F = 0.65, df = 1.34, p = 0.466). The frequencies of complications in the treatment groups were similar. Resveratrol administration for a duration of 8 weeks improved characteristic symptoms in patients with ADHD according to their parents. Further investigations containing larger sample sizes, longer supplementation periods, and dose–response evaluations are required to replicate these findings in ADHD children more confidently. [ABSTRACT FROM AUTHOR]