The impact of bilirubin levels on wound healing remains a topic of controversy. The present study is a literature review that examines the impact of increased levels of bilirubin in the bloodstream on the process of wound healing. The physiological pathways and their interrelationships, as well as the relevant research publications, were comprehensively addressed in our discussion. The present study undertook a comprehensive review of the extant literature pertaining to the impact of bilirubin concentration on the process of wound healing, with particular emphasis on its association with reactive oxygen species. This scholarly article provides an overview of several studies that elucidate the mechanisms and correlation between bilirubin and the process of wound healing. The impact of bilirubin on wound healing has been observed, and it appears to function as a modulator. This review demonstrates that there exists a spectrum of bilirubin concentrations that can function as precise regulators, although this range falls under pathological hyperbilirubinemia. Further research is required to determine the precise boundary of this range. Within a certain range, bilirubin serves as a positive regulator in the process of wound healing. Beyond this range, it has the potential to function as a negative regulator. Significance statement Bilirubin, a derivative resulting from the breakdown of heme, plays a crucial role in safeguarding cellular integrity. The potential significance of bilirubin's biological functions in mitigating oxidant‐induced cellular apoptosis is noteworthy. Specifically, the administration of bilirubin at a low concentration has been shown to effectively scavenge reactive oxygen species. The application of topical bilirubin has the potential to enhance wound healing, thereby augmenting the therapeutic utility of bilirubin.