Abstract <p>Reactive oxygen species regulate many biological processes and need constant surveillance and fine-tuning. Oxidative stress can result in the initiation &amp; progression of various cancers including Head and Neck Cancers [HNCs]. The diversity in the structure of the phytochemicals enable them to modulate the redox homeostasis at molecular, biochemical &amp; cellular levels. Understanding the redox regulatory mechanisms induced by phytochemicals is of interest to develop therapeutics against cancers, especially head and neck cancers. Phytochemicals offer multiple benefits compared to synthetic drugs, such as being more affordable, having fewer or no side effects, and being more accessible to the general population. Targeted therapies including immunotherapies, oral microbiome as well as phytochemicals are important factors in the prevention and treatment of HNC. Phytochemicals, besides having chemopreventive &amp; chemotherapeutic role in cancer, can also modulate microbiota indirectly influencing the therapeutic outcome. Despite advancements in therapeutic modalities and emergence of new therapies, management and treatment of HNC is still elusive. Heterogeneity, poor prognosis, invasiveness, and resistance to conventional therapies have been the major road blocks. This review aims to explore and identify new therapeutic approaches for addressing targets linked to redox imbalances. The use of phytochemicals to modulate redox homeostasis at almost all stages of HNC can give a better opportunity for early detection, and prevention leading to improved quality of life for patients. Further development of probes that can detect ROS, for precise therapeutic outcome of phytochemical treatments can also be an important strategy.</p> Graphical abstract <p></p>