Conventional therapies for oral squamous cell carcinoma (OSCC), a serious worldwide health problem, are frequently constrained by inadequate targeting and serious side effects. Drug delivery systems (DDS) based on nanoparticles provide a possible substitute by improving drug stability, target accuracy, and lowering toxicity. By addressing issues like irregular vasculature and thick tumor matrices, these methods allow for more effective medication administration. For instance, the delivery of cisplatin via liposomes, as opposed to free drug formulations, results in a 40% improvement in tumor suppression. Likewise, compared to traditional techniques, poly (lactic-co-glycolic acid) (PLGA) nanoparticles can produce up to 2.3 times more intertumoral drug accumulation. These platforms have effectively administered natural substances like curcumin and chemotherapeutics like paclitaxel, enhancing therapeutic results while reducing adverse effects. Despite their promise, several types of nanoparticles have drawbacks. For example, PLGA nanoparticles have scaling issues because of their complicated production, whereas liposomes are quickly removed from circulation. In preclinical investigations, functionalized nanoparticles-like EGFR-targeted gold nanoparticles-improve selectivity and effectiveness by obtaining up to 90% receptor binding. By preferentially accumulating in tumors via the increased permeability and retention (EPR) effect, nanoparticles also improve immunotherapy and radiation. Mechanistically, they increase the death of cancer cells by causing DNA damage, interfering with cell division, and producing reactive oxygen species (ROS). There are still issues with toxicity (such as the buildup of metallic nanoparticles in the liver) and large-scale manufacturing. Nevertheless, developments in multifunctional platforms and stimuli-responsive nanoparticles show promise for getting over these obstacles. These developments open the door to more individualized and successful OSCC therapies.