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Background Osteoarthritis (OA) is a whole-joint disease driven by complex immunopathogenic mechanisms and chronic inflammation, positioning platelet-rich plasma (PRP) as an emerging therapy of significant interest. Objective This study conducts a bibliometric analysis to systematically map the global research landscape, hotspots, and immunological trends of PRP for the treatment of OA from 2004 to 2024. Methods We analyzed 1,862 articles and reviews retrieved from the Web of Science Core Collection (WoSCC) for bibliometric mapping, complemented by 148 clinical trial records from PubMed for qualitative analysis. We utilized VOSviewer, CiteSpace, and the R-package bibliometrix for visual analysis of countries, institutions, authors, journals, and keywords. Results The results demonstrate a significant growth in annual publication volume since 2012, with the United States (1,675 publications) and China (1,310 publications) being the most productive countries. The Rizzoli Orthopaedic Institute, the Hospital for Special Surgery, and Rush University were identified as core research institutions, while Giuseppe Filardo was the most prolific author. The American Journal of Sports Medicine ranked as the leading journal in both publication count and total citations. Keyword analysis identified four major research hotspots: disease targets and tissue mechanisms, pathophysiological processes, comparative clinical treatments, and research methodologies. Recent research frontiers include “macrophage polarization” and “exercise.” Conclusion This study provides bibliometric evidence that the research landscape of PRP for OA is transitioning from a focus on tissue regeneration to immunomodulation. The field has evolved from observing clinical outcomes to unraveling the intricate immune-mediated mechanisms, particularly the regulation of macrophage phenotypes and inflammatory mediators. Future research should prioritize standardizing PRP protocols based on their immunomodulatory potential and further exploring strategies to precisely manipulate the joint inflammatory environment for therapeutic gain.