Specific nutraceuticals including omega-3 fatty acids, coenzyme Q10, polyphenols, and isothiocyanates demonstrate neuroprotective effects by targeting oxidative stress, neuroinflammation, and mitochondrial dysfunction — three key drivers of age-related cognitive decline. The gut microbiota emerges as a critical mediator, directly influencing the bioavailability and efficacy of these compounds through the microbiota-gut-brain axis. This convergence represents a significant shift from traditional symptom-focused pharmaceutical approaches toward prevention-oriented interventions. The practical implications are substantial for aging adults seeking evidence-based cognitive protection strategies. Unlike single-target drugs, these compounds offer multi-pathway protection with established safety profiles. However, this narrative review format limits definitive clinical guidance — the field still lacks large-scale human trials with standardized dosing protocols. The most intriguing aspect involves personalized microbiome profiling to optimize individual nutraceutical responses, suggesting future precision medicine applications. While the mechanistic rationale is compelling and the risk-benefit profile favorable, translating these promising laboratory findings into reliable clinical protocols remains the critical next step for practical cognitive health applications.