Osteosarcoma (OS) is a prevalent primary malignant bone tumor, typically managed through a combination of neoadjuvant chemotherapy and surgical interventions. Recent advancements in early detection and the use of novel chemotherapeutic agents have significantly improved the 5-year survival rate of OS patients. However, some patients fail to achieve the desired treatment outcomes despite undergoing intensive chemotherapy and surgical procedures, with chemotherapy resistance emerging as a critical factor contributing to therapeutic failure in OS. Noncoding RNAs (ncRNAs) are a group of RNAs that lack protein-coding capacity but play a crucial role in tumor progression by modulating various biological characteristics of cancer cells, such as proliferation, apoptosis, migration, invasion, and drug resistance. Emerging evidence indicates that the dysregulated expression of numerous ncRNAs in OS cells can influence the response to chemotherapeutic agents by modulating processes such as cell apoptosis, signaling pathways, intracellular drug concentrations, and cell autophagy. This review aims to elucidate the roles and mechanisms of ncRNAs in mediating drug resistance in OS, offering new insights for investigating novel pathways underlying drug resistance, overcoming tumor resistance to therapeutics, and developing innovative chemotherapeutic strategies.