The use of liquid biopsy in cancer research has grown exponentially, offering potential for early detection, treatment stratification, and monitoring residual disease and recurrence. Exosomes, released by cancer cells, contain tumor-derived materials and are stable in biofluids, making them valuable biomarkers for clinical evaluation. Bibliometric research on osteosarcoma (OS) and exosome-derived diagnostic biomarkers is scarce. Therefore, we aimed to conduct a bibliometric evaluation of studies on OS and exosome-derived biomarkers. Using the Web of Science Core Collection database, Microsoft Excel, the R "Bibliometrix" package, CiteSpace, and VOSviewer software, quantitative analyses of the country, author, annual publications, journals, institutions, and keywords of studies on exosome-derived biomarkers for OS from 1995 to 2023 were performed. High-quality records (average citation rate ≥ 10/year) were filtered. The corresponding authors were mainly from China, the USA, Australia, and Canada. The University of Kansas Medical Center, National Cancer Center, Japan, and University of Kansas were major institutions, with limited cooperation reported by the University of Kansas Medical Center. Keyword analysis revealed a shift from cancer progression to mesenchymal stem cells, exosome expression, biogenesis, and prognostic biomarkers. Qualitative analysis highlighted exosome cargo, including miRNAs, circRNAs, lncRNAs, and proteins, as potential diagnostic OS biomarkers. This research emphasizes the rapid enhancement of exosomes as a diagnostic frontier, offering guidance for the clinical application of exosome-based liquid biopsy in OS, contributing to the evolving landscape of cancer diagnosis.