Saliva is secreted by the salivary exocrine glands that primarily aids in the lubrication and protection of the oral cavity. Disease conditions leading to the degeneration of the glandular tissue cause severe hyposalivation, which affects the overall health of the patients. Currently available treatment options for hyposalivation are mostly palliative and do not tackle the cause of the disease, therefore many studies are now focusing on stem cell-based regenerative therapies to restore gland function. Earlier studies in mouse submandibular gland have identified K14 expressing ductal stem cells, as the only stem cell population in the gland, however, our knowledge about the existence and function of ductal stem cells in parotid and sublingual glands is very limited. Since all three major salivary glands are the major contributors to the secretion of saliva in oral cavity, it is important to understand the mechanism of cell renewal and regeneration in all salivary glands, so as to develop an effective treatment for hyposalivation. Here, using genetic labeling and fate map analysis we show that K14-expressing ductal stem cells are present in the adult parotid gland and contribute to maintenance of ductal cells during steady-state conditions. In the sublingual gland, however, although K14-expressing ductal cells are present, they do not display characteristics of tissue stem cells. We found that in response to a severe injury, regeneration of the sublingual gland is mediated by myoepithelial cells that show remarkable plasticity by dedifferentiating to acinar cells. These studies reveal the similarities and differences in the role of ductal stem cells among the major salivary glands and widens the treatment options for each salivary gland type.