Osteosarcoma is the most frequent bone malignancy in children and adolescents. Despite advances of surgery and chemotherapy in osteosarcoma over the past decades, overall survival rates of osteosarcoma have reached a plateau. The development of multi-drug resistance (MDR) has become the main obstacle in improving chemotherapeutic effects in osteosarcoma treatment. Therefore, understanding detailed mechanisms of chemoresistance and developing novel therapeutic targets to overcome chemoresistance are crucial to improve the prognosis of osteosarcoma patients. Accumulating evidence has proved that multiple noncoding RNAs (ncRNAs), including microRNAs (miRNAs), long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) play pivotal roles in osteosarcoma progression. Notably, a great number of ncRNAs are abnormally expressed and can regulate chemosensitivity through various mechanisms in osteosarcoma. In this review, we systematically summarize the roles of ncRNAs as well as the molecular mechanisms in modulating drug resistance of osteosarcoma and discuss the potential roles of ncRNAs as biomarkers and novel therapeutic targets for osteosarcoma.