<p>Oral squamous cell carcinoma (OSCC) is one of the very prominent types of proliferative malignant tumor and experiences poor prognosis in addition to recurrence. The available therapeutic approaches that have been developed to manage OSCC include surgery, chemotherapy (using agents like cisplatin and carboplatin), radiotherapy, and immunotherapy. These approaches are not always effective and have negative side effects. Recently, to improve therapeutic efficacy at target location as well as lower systemic toxicity, the latest developments in the nanomedicine for the treatment of OSCC have emphasized developing specific drug delivery systems using nanoparticles such as pro-niosomes, niosomes, transferosomes, phytosomes, aquasomes, etc. Ligand-conjugated nano-liposomes have been included in the most promising drug delivery approaches for the precise distribution of herbal bio-actives (such as curcumin, artemisinin, etc.) in the management of OSCC. Nanoliposomes have multitudinous benefits as nanocarriers due to their structural similarity with the biological membranes, along with their biocompatibility, biodegradability, and safety. This review focuses on the underlying causes of OSCC, alterations in the signalling pathways, and potential benefits of bio-actives loaded vesicular delivery carriers including extracellular vesicles, liposomes, etc. Along-side, possible applications of nanoliposomes and surface modification on nanoliposomes with ligands like folic acid, cetuximab, etc., that help to protect nanoliposomes from the mononuclear phagocytic system, enhancing their half-life and enabling targeted delivery to overexpressed receptors in the OSCC are discussed.</p> Graphical Abstract <p></p>