ABSTRACT Objectives: Polyphenols, particularly anthocyanins, have received attention in improving health issues during old age, including decline in cognitive function and other health parameters. We aimed to determine the effects of polyphenols-rich tropical fruit TP 3-in-1™ juice towards improving cognitive function, oxidative stress and metabolomics profiles among middle-aged women. Methods: This clinical trial involved 31 subjects with signs of poor cognitive function, as assessed using the Rey Auditory Verbal Learning Test (RAVLT). They were randomized to receive either TP 3-in-1™ juice (n = 16) or placebo (n = 15). Study subjects consumed 500 ml of beverages for three times per day, three days per week, for a period of ten weeks. Juice supplementation provided 9135 mg GAE of total phenolic content and 194.1 mg cyanidin-3-glucoside of total anthocyanin monomer. Results: There was a significant interaction effects on RAVLT immediate recall (p < 0.05) and Comprehensive Trail Making Test (CTMT) Trail 4 (p < 0.05). Metabolomics analysis showed the presence of metabolites related to polyphenols intake and cognitive functions with the intervention group showed increased urinary excretion of thyroxine and 3-methyladenine. Thyroxine and 3-methyladenine give stability to human transthyretin (TTR) and activate autophagy, respectively, which are associated with the pathogenesis of Alzheimer’s disease. Conclusion: The result shows the potential of TP 3-in-1™ juice which is rich in anthocyanins in improving cognitive function, particularly learning, memory, processing speed, sequencing, mental flexibility and visual-motor skills domains, among middle-aged women.