Introduction. Aging involves in a series of deterioration including: brain shrinkage (e.g. loss of neurons and plasticity) and declines in cognitive and physical functions (e.g. memory loss, reduced gait and balance, and loss of muscle mass and strength). Long-term exercise training and dietary supplementation have been shown to attenuate and improve these age-related declines in cognitive and physical functions in older individuals. A commercially available multi-ingredient dietary supplement, MindWorks® (Shaklee, CA), consists of vitamins B6, vitamin B12, folate, chardonnay grape extract, guarana extract, blueberry powder and green coffee extract, all of which have been reported to maintain or improve in brain function, cognition, cardiovascular function, and gait speed in older adults; however, existing results in human studies remain inconsistent. Another therapeutic intervention such as Tai Chi exercise has been shown to improve cognitive performance (e.g. short-term memory, working memory, and semantic memory), and physical function (e.g. gait, balance, flexibility, and blood pressure) in older adults although the underlying mechanisms are undetermined. The main objective of the present study was to demonstrate the impact of MindWorks® supplementation on cognitive and physical functions in middle-aged and older healthy individuals in comparison to a placebo (as negative control) and Tai Chi exercise (as positive control). The central hypothesis was that MindWorks® supplementation and Tai Chi exercise would improve cognitive and physical functions in middle-aged and older individuals compared to placebo group. Specific aim 1 was to examine the extent to which 12 weeks of MindWorks® supplementation and Tai Chi training would differentially affect cognitive function by measuring animal naming test (ANT) and digital span test (forward digit span, FDS, and backward digit span, BDS), and physical function by measuring Tandem Romberg test, single leg stance (SLS) test, dynamic balance test via the Biodex Balance System (BBS), timed up and go test (TUG), and functional reach test (FRT) in middle-aged and older individuals in comparison to placebo. Specific aim 2 was to determine the degree to which 12 weeks of MindWorks® supplementation and Tai Chi training would improve blood pressure, heart rate (HR), and blood biomarkers known to be involved in the pathogenesis of cognitive and cardiovascular dysfunction including homocysteine, vitamins B6, vitamin B12, folic acid, brain-derived neurotrophic factor (BDNF), and nitric oxide (NO). Methods. This was a randomized, double-blind, placebo-controlled study. Healthy middle-aged and older men and postmenopausal women (45-75 years old, N=75) were randomly assigned to one of three experimental groups: 1) MindWorks® supplementation (MW), 2) placebo tablet supplementation (PL), or 3) Tai Chi training (EX). The participants in the supplementation group took 1 tablet daily (MindWorks® or placebo) with a meal in the morning for 12 weeks. The participants in the Tai Chi group performed the simplified 24-form Yang Tai Chi exercise program (3x/week) for 12 weeks. Dependent variables were measured at pre- and post-intervention time points to investigate changes in cognitive, physical, and cardiovascular functions, and cognitive and cardiovascular related biomarkers. Data were analyzed using a 3×2 (treatment by time) mixed ANOVA followed by Bonferroni post-hoc analyses when a significant F value was observed. Results. EX group showed significant improvements in physical function measures at pre- and post-intervention time points in SLS test (+43.13%, p= 0.025), BBS dynamic test level 2 anterior/posterior scores (+58.43% improvement, p= 0.001), and TUG test (-14%, p< 0.001). MW group showed a significantly increase in BDNF levels after 12-week supplementation (+33.07%, p= 0.004). Both MW and EX group had significantly improved physical health scores (PHS) in SF-36 survey (MW: +5.05%, p= 0.035; EX: +9.04%, p= 0.009) after the interventions. Additionally, comprehensive falls risk screening instrument (CFRSI) revealed that participants in all three groups were at low risk of falls category at pre- and post-intervention time points. Three-day food record revealed participants in all three groups had sufficient vitamin B6, B12, folic acid consumption at pre- and post-intervention time points. Conclusion. The 12 weeks of multi-ingredient dietary (MindWorks®) supplementation and Tai Chi training were beneficial to middle-aged and older adults on different cognitive and physical function domains with improved self-perception of health status. While Tai Chi training noticeably improved physical functions including gait, static and dynamic balance, enhanced BDNF levels in MW group implied that MindWorks® supplementation potentially promotes neuroprotective effects during aging process.