Immune-mediated oral disorders are characterised by their chronicity, and some are refractory to treatment. Interference RNA (iRNA) has been implicated in the underlying mechanism of such immune-mediate oral and refractory inflammatory oral diseases. iRNA-based understanding of the mechanism in these diseases may help to produce non-invasive diagnostic methodologies and treatment modalities of such drug non-responsive diseases. Oral lesions in these immune-mediated diseases can precede the occurrence of lesions in other regions of the body. The early diagnosis and treatment of these drug non-responsive diseases might benefit the patient by reducing chronicity and probably even resolving the disease. This aim of the present minireview is to give an overview of the possible implications of iRNA on the pathogenesis, diagnosis, and treatments of immune-mediated and inflammatory oral diseases. The manuscript can form the framework for research on iRNA in these immune-mediated oral disorders.