<p>Osteosarcoma (OS) is recognized as the most prevalent primary malignant bone tumor, characterized by rapid progression, early metastasis, limited efficacy of conventional chemotherapy or radiotherapy, and unfavorable clinical outcomes. Recent studies have highlighted the critical role of non-coding RNAs (ncRNAs), including microRNAs, long non-coding RNAs, and circular RNAs, in the regulation of osteosarcoma biology. The altered expression of these molecules significantly influences tumor cell proliferation, migration, apoptosis, and angiogenesis. Moreover, their dysregulation has been associated with drug resistance and disease recurrence. Given these attributes, ncRNAs are emerging as potential biomarkers for both diagnosis and prognosis, as well as promising therapeutic targets. A more profound understanding of their molecular mechanisms may aid in the development of more effective and personalized strategies for managing osteosarcoma.</p> Graphical Abstract <p></p>