A single daily oral dose of sertraline for four weeks led to multiple histological changes in the submandibular salivary glands of albino rats. Sertraline induced a massive increase in the total protein content in the tissues of submandibular salivary gland as diagnosed by Sodium dodecyl sulfate polyacrylamide gel electrophoresis. Stereoscopic and electron microscopic examination of the effect of sertraline on the rat molars revealed the extension of caries to all grooves, surfaces and even roots. After cessation of sertraline for two weeks, there was reduction in the vacuolation of the serous acini, striated, excretory ducts and granular convoluted tubules. Also, there was an increase in the number of inflammatory cells. After cessation of sertraline for two weeks, there was a decrease in the total protein content of the submandibular salivary gland as recorded by Sodium dodecyl sulfate polyacrylamide gel electrophoresis. After cessation of sertraline for two weeks, areas of remineralization and repair were detected on the occlusal surface by the scanning electron microscope.