Few topical formulations have been designed specifically to treat oral mucosal diseases. Local drug delivery may provide a more targeted and efficient option than systemic delivery for diseases of the oral mucosa. The permeability to the topical drugs differs according to the thickness of the epithelium and the extent of keratinization. The loss of the permeability barrier in the oral mucosa, due to ulceration or erosion, leads to rapid diffusion of the drug into tissues as compared to the intact areas of the mucosa. Oral mucosal delivery has the potential to treat many different conditions and diseases, such as oral cancer, mucositis, lichen planus, herpes simplex, candidiasis, recurrent aphthous stomatitis, vesiculo-bullous diseases, neuropathic pain and salivary dysfunction. Each therapy requires distinct penetration and drug retention profiles in order to optimize treatment and minimize side effects. In this paper, topical medications are discussed, as these are advantageous for the treatment of oral mucosal lesions with fewer side effects.