Context:The aim of this systematic review was to evaluate clinical trial data regarding the effect of resveratrol supplementation on cognitive performance and mood in populations that are healthy and in the clinical setting. Data Sources:Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic literature review of randomized controlled trials was conducted. Data Extraction:A meta-analysis was also conducted to determine treatment effect on the following cognitive domains and mental processes: processing speed, number facility, memory, and mood. Risk of bias was assessed using the Cochrane Collaboration Risk of Bias tool. Quality of the body of evidence was assessed by evidence for each outcome related to cognitive function for which data was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE). Results:Ten studies were included. Three studies found resveratrol supplementation significantly improved some measures of cognitive performance, 2 reported mixed findings, and 5 found no effect. When data were pooled, resveratrol supplementation had a significant effect on delayed recognition (standardized mean difference [SMD], 0.39; 95% confidence interval [CI], 0.08-0.70; I2 = 0%; P = 0.01; n = 3 studies; n = 166 participants) and negative mood (SMD, -0.18; 95%CI, -0.31 to -0.05; I2 = 0%; P = 0.006; n = 3 studies; n = 163 participants). Included studies generally had low risk of bias and were of moderate or high quality. Conclusions:The results of this review indicate that resveratrol supplementation might improve select measures of cognitive performance; however, the current literature is inconsistent and limited.