Reactive oxygen species (ROS) is considered a double-edged sword. The slightly elevated level of ROS helps in wound healing by inhibiting microbial infection. In contrast, excessive ROS levels in the wound site show deleterious effects on wound healing by extending the inflammation phase. Understanding the ROS-mediated molecular and biomolecular mechanisms and their effect on cellular homeostasis and inflammation thus substantially improves the possibility of exogenously augmenting and manipulating wound healing with the emerging antioxidant therapeutics. This review comprehensively delves into the relationship between ROS and critical phases of wound healing and the processes underpinning antioxidant therapies. The manuscript also discusses cutting-edge antioxidant therapeutics that act via ROS scavenging to enhance chronic wound healing.