Plant-derived antioxidants represent a diverse array of bioactive compounds with significant therapeutic potential across multiple disease states. This review critically examines the molecular mechanisms underlying antioxidant activity, including free-radical scavenging, metal chelation, and modulation of cellular redox signaling pathways. We evaluate the translational applications of polyphenols, flavonoids, carotenoids, and related phytochemicals in cancer prevention, cardiovascular disease, neurodegeneration, and metabolic disorders. Despite promising preclinical evidence, clinical translation faces substantial challenges related to bioavailability, metabolic stability, and pharmacokinetic variability. Emerging formulation strategies, including nanoencapsulation and structural modification, offer promising solutions to enhance therapeutic efficacy. This comprehensive analysis highlights the current state of knowledge, identifies critical gaps in translational research, and proposes future directions for developing plant-derived antioxidants as evidence-based therapeutic agents.