INTRODUCTION: Nanotechnology has shown potential in treating different types of cancers. In particular, nano-drug delivery systems (DDSs) offer a promising strategy for treating oral cancer. By customizing therapy and improving drug delivery, these systems can improve outcomes for patients. Hence, a review was conducted to assess the current evidence and explore the use of DDSs for treating oral cancer. AIM: To comprehensively explore the nano-drug carriers and target delivery for oral cancer therapy and to discuss the benefits, challenges, and potential to guide future research and clinical practice. METHODOLOGY: A systematic search of articles archived in PubMed, Scopus, and Cochrane using keywords such as Nano, drug carrier, target drug delivery, and oral cancer was performed to fulfill the objectives from inception till February 2, 2024. Articles providing insights into nano-drug carriers in oral cancer were included. RESULTS: The results revealed a total of 156 articles. After duplicate removal, 136 articles were screened for title and abstract as per the inclusion and exclusion criteria. A total of 113 articles were excluded with reasons. Out of the remaining 23 articles, only 11 were included for qualitative data synthesis. CONCLUSION: The literature revealed scarcity of oral cancer-related work using DDSs. Qualitative synthesis of data revealed that nano-drug carriers demonstrated a promising avenue for targeted therapeutic approaches in oral cancer, despite the challenges and their potential benefits. Continued research and development in this field are crucial to overcoming these challenges and fully realizing the potential of nano-drug carriers in revolutionizing oral cancer therapy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12663-024-02251-z.