The Mediterranean diet is associated with reduced mortality and cognitive decline, largely due to its polyphenol content. However, Western populations often do not meet recommended fruit and vegetable intakes. Polyphenols exert anti-inflammatory effects and may influence extracellular vesicle (EV) dynamics. DailyColors™ is a polyphenol-rich blend inspired by the Mediterranean Diet, containing extracts from 16 fruits, vegetables, and herbs. This 60-day, double-blind, placebo-controlled, randomised trial involved 150 UK adults aged 50+ with a BMI ≥ 25, recruited to complete cognitive and physical fitness assessments via the PROTECT-UK online platform. Participants received either a medium (750mg) or high (2000mg) dose of DailyColors™ (~300mg and ~750mg polyphenols, respectively) or a placebo. A sub-group (n=15 per group) underwent additional assessments, including blood pressure measurements, characterisation of circulating EVs and tandem-mass-tagged serum proteomics. Significant cognitive benefits were observed, with improvements in reaction time for the high-dose group and accuracy for both active supplement groups. The high-dose group also showed significant physical fitness gains on the Timed Stand Test (P<0.001). All groups improved on the Chair Stand Test. Proteomic analysis showed significantly reduced serum protein expression in immune and pre-β1-HDL pathways, suggesting anti-inflammatory effects. Pre-β1-HDL proteins are typically elevated in obesity; their reduction suggests a reversal of this obesity-related effect. No significant changes were noted in EV concentration or size. DailyColors™ supplementation, may enhance cognitive function, physical fitness, and systemic health in older, overweight adults, potentially mimicking the anti-inflammatory effects of the Mediterranean diet. These findings warrant investigation in larger trials.