Oral cancer is one of the most common cancers worldwide, of which more than half of patients are diagnosed at a locally advanced stage with poor prognosis due to recurrence, metastasis and resistant to treatment. Thus, it is imperative to further explore the potential mechanism of development and drug resistance of oral cancer. Exosomes are small endosome-derived lipid nanoparticles that are released by cells. Since the cargoes of exosomes were inherited from their donor cells, the cargo profiles of exosomes can well recapitulate that of their donor cells. This is the theoretical basis of exosome-based liquid biopsy, providing a tool for early diagnosis of oral cancer. As an important intracellular bioactive cargo delivery vector, exosomes play a critical role in the development of oral cancer by transferring their cargoes to receipt cells. More importantly, recent studies have revealed that exosomes could induce therapy-resistance in oral cancer through multiple ways, including exosome-mediated drug efflux. In this review, we summarize and compare the role of exosomes in the diagnosis, development and therapy-resistant of oral cancer. We also highlight the clinical application of exosomes, and discuss the advantages and challenges of exosomes serving as predictive biomarker, therapy target and therapy vector in oral cancer.