Wound healing is a complex biological process encompassing haemostasis, inflammation, proliferation and matrix remodelling. Reactive oxygen species (ROS) play a pivotal role in regulating key events such as antimicrobial defence, platelet activation and angiogenesis. However, excessive ROS levels can induce oxidative stress (OS), disrupting the healing cascade and contributing to chronic wounds, inflammation and impaired tissue repair. Systemic conditions like diabetes, obesity, smoking and ageing further exacerbate OS, highlighting its clinical significance in wound management. Antioxidants (AOx), both endogenous and exogenous, have demonstrated therapeutic potential in mitigating OS, promoting wound closure and enhancing cellular recovery. Compounds like Vitamin E, curcumin, ferulic acid and resveratrol improve AOx enzyme activity, reduce oxidative damage and accelerate wound healing in multiple studies. Emerging evidence supports targeting oxidative pathways as a viable strategy to improve outcomes in chronic and systemic OS-related conditions. This review explores the dual role of ROS in wound healing, the impact of OS in systemic diseases, and the therapeutic potential of AOx in fostering optimal healing outcomes, advocating for robust clinical trials to establish standardised interventions.