Oxidative stress, defined by an imbalance between the generation of reactive oxygen species and the capacity of biological systems to detoxify these reactive intermediates, plays a central mechanistic role in the pathogenesis of numerous chronic disorders, including cardiovascular diseases, neurodegenerative conditions, diabetes mellitus, and various malignancies. Conventional therapeutic strategies targeting oxidative stress have been largely limited by the inadequacy of single-target antioxidant agents, unfavorable pharmacokinetic profiles, and insufficient clinical efficacy in advanced disease states. In this context, phytochemicals — bioactive secondary metabolites derived from plant sources — have emerged as a structurally diverse and mechanistically versatile class of compounds capable of addressing multiple dimensions of oxidative injury. This review examines the molecular basis of oxidative stress, characterizes the major classes of phytochemicals with antioxidant activity, and critically evaluates the mechanisms through which these compounds exert cytoprotective effects, including direct free radical scavenging, activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling axis, modulation of inflammatory mediators, and preservation of mitochondrial integrity. Evidence from preclinical experimental models and emerging clinical investigations is synthesized to assess the therapeutic relevance of phytochemical interventions. Challenges pertaining to bioavailability, standardization, and regulatory frameworks are discussed alongside recent advances in delivery technologies that enhance the translational potential of plant-derived antioxidants. The review concludes by identifying key research priorities and future directions for integrating phytochemical-based therapies into evidence-based medicine for oxidative stress-related disorders.