<p>Zinc homeostasis is associated with the severity of ischemia-reperfusion injury (IRI). This study provides a bibliometric analysis of global research trends in this field. A total of 1,439 publications from 2000 to 2025 were retrieved from the Web of Science Core Collection and Scopus databases. Data visualization and knowledge mapping were conducted using VOSviewer, CiteSpace, and the R package bibliometrix to analyze collaborative networks, citation bursts, and keyword clusters. Annual publication output increased over the 25-year period, reaching a peak of 83 articles in 2022. The growth follows the exponential model y = 32.378e^0.0361x. China leads in publication volume with 527 articles, while the United States has the highest total citation count of 31,368. Germany recorded the highest average citation rate of 195.90 per publication. Keyword analysis indicates a shift in research focus from foundational mechanisms, such as oxidative stress and superoxide dismutase, to current frontiers including Nrf2 signaling, ferroptosis, and the regulation of zinc transporters. Zinc serves as an intracellular signaling mediator in the context of IRI. Despite robust preclinical evidence, a translational gap persists due to pharmacokinetic differences, therapeutic timing, and the lack of clinical trials in <i>ClinicalTrials.gov</i>. Future research priorities include the development of targeted nanomedicines and metallomics-based patient stratification to improve outcomes in myocardial infarction, stroke, and organ transplantation.</p>