Background/Objective <p>The global aging population presents significant health and societal challenges, driven by age-related disorders including neurodegeneration, cardiovascular disorders, and metabolic syndromes. Phytochemicals show promise in promoting healthy aging and longevity. This study explores their multifaceted roles in mitigating aging hallmarks through molecular, epigenetic, and gut microbiota interactions.</p> Methods <p>A comprehensive review of current literature (2017–2024) published in PubMed and Scopus, using keywords such as phytochemicals, longevity and aging was conducted, focusing on the biological activities of phytochemicals, their molecular mechanisms, and their role in modulating key aging pathways such as AMP-activated protein kinase (AMPK), the mechanistic target of rapamycin (mTOR), and sirtuins. The interaction among phytochemicals and epigenetics, gut microbiome, and their bioavailability challenges were also analyzed.</p> Results <p>Phytochemicals exhibit potent antioxidant, anti-inflammatory, and senolytic properties, targeting aging characteristics such as oxidative stress and cellular senescence. Compounds like resveratrol and quercetin influence epigenetic regulation, while others modulate gut microbiota, enhancing therapeutic efficacy. Despite their potential, low bioavailability and interindividual variability remain critical challenges. Emerging delivery systems and personalized approaches show promise for optimizing their benefits.</p> Conclusion <p>Phytochemicals offer a natural, integrative strategy to promote longevity and mitigate age-related diseases by targeting fundamental aging mechanisms. Advancements in clinical validation, bioavailability enhancement, and personalized nutrition are essential to harness their full potential, paving the way for transformative applications in healthy aging interventions.</p>