Abstract Introduction The bisphosphonates are drugs known by their antiresorptive potency and are widely prescribed for treating and preventing osteoporosis. In the past years the employment of this class of drugs had spread to other pathologies, and it is being prescribed to patients in a wide range of ages. Some adverse effects of bisphosphonate treatment have been highlighted recently, however, little is known about its potential side effects in salivary glands. Methods Newborn rats received daily doses of 2.5mg/kg/day of sodium alendronate during 30 days. On the thirtieth day the animals were stimulated with pilocarpine and their parotid and submandibular glands were collected, fixed and embedded for histological and ultrastructural analysis. Some glands were collected for analysis of protein content and amylase activity. Results At light microscopy, the alendronate-treated animals presented an accumulation of secretion granules in their cytoplasm, which was confirmed by the ultrastructural examination. Biochemical analysis revealed an increase in total protein content and decreased amylase levels of both glands in the alendronate-treated animals in relation to the control. Conclusion Based on the current findings, alendronate is probably interfering in secretory pathways of parotid and submandibular glands.