Antioxidants neutralize reactive oxygen species and free radicals, protecting cells from oxidative damage and maintaining cellular homeostasis. In cancer therapy, they play a complex dual role, serving as protective agents against oxidative stress while, under certain conditions, acting as pro-oxidants that may promote tumorigenesis and resistance to treatment. Redox regulation is governed by key antioxidant pathways, such as the BACH1 and NRF2 pathways, along with transcriptional factors that significantly affect cancer progression and immunotherapy response. In addition to their intracellular effects, antioxidants modulate the tumor microenvironment, including interactions with the extracellular matrix, which impact cancer cell behavior and therapeutic responses. This review also explores preclinical studies that investigate the roles of major antioxidants in cancer biology. While these studies present promising data, significant challenges persist, including the potential for antioxidants to interfere with standard cancer treatments or to inadvertently support tumor survival. We further highlight emerging strategies aimed at optimizing antioxidant therapy, including personalized medicine approaches, nanoparticle-based delivery systems, and combination treatments with immunotherapies and targeted therapies. By examining the therapeutic potential and associated risks of antioxidants, this review provides critical insights into their role in cancer treatment and offers a roadmap for advancing antioxidant-based strategies to improve clinical outcomes.