Growing evidence supports the synergistic benefits of combining dietary polyphenols with physical exercise in enhancing brain health and mitigating the progression of glioma. Both interventions independently exert neuroprotective and anticancer effects through mechanisms involving antioxidant activity, anti-inflammatory pathways, and epigenetic regulation. This review explores the integrated impact of polyphenol supplementation and exercise on brain well-being, with a particular focus on epigenetic modifications, cognitive function, and the processes of learning and memory. Polyphenols such as curcumin, resveratrol, quercetin, and epigallocatechin-3-gallate have been shown to modulate key epigenetic mechanisms, including DNA methylation, histone modification, and noncoding RNA expression, resulting in the regulation of genes involved in neurogenesis, synaptic plasticity, and gliomagenesis. Concurrently, physical exercise induces epigenetic remodeling that enhances neuroplasticity, improves mitochondrial function, and stimulates the expression of neurotrophic factors, notably brain-derived neurotrophic factor. The convergence of these two interventions may offer a powerful, nonpharmacological approach to improve cognitive performance, slow neurodegeneration, and inhibit glioma growth by restoring tumor suppressor gene activity and attenuating oncogenic signaling. This review synthesizes current preclinical and clinical findings and highlights the therapeutic potential of combining polyphenols and exercise within a predictive and preventive framework. The integration of nutritional neuroscience with lifestyle medicine opens new avenues for targeted interventions aimed at preserving cognitive health and managing brain malignancies.