Declined salivary gland function is commonly observed in patients with diabetes. Advanced glycation end products (AGEs) are believed to contribute to the pathogenesis of diabetes-induces hypofunction of the salivary glands. Polydatin (resveratrol-3-O-β-mono-D-glucoside) is a polyphenol that can be easily accessed from peanut, grape, and red wines. Although polydatin is known to have anti-glycation, anti-oxidation, and anti-inflammation effects, its effect in the salivary gland is not known. In the present study, we evaluated the AGEs burden in the salivary gland in streptozotocin (STZ)-induced diabetic rats and the protective effect of polydatin on diabetes-related salivary hypofunction. Polydatin (50 and 100 mg/kg/day) was orally administered in the STZ-induced diabetic rats for 4 weeks. The results showed that the salivary flow rate of the STZ-induced diabetic rats was reduced compared with that in the normoglycemic control rats. The circulating AGEs in serum and secreted AGEs in saliva increased in the STZ-induced diabetic rats. The reactive oxygen specises (ROS) were highly generated in the salivary gland in these diabetic rats. The salivary gland from the diabetic rats showed increased acinar cell apoptosis compared to normoglycemic control mice. However, polydatin suppressed all of these diabetes-related salivary changes. Overall, polydatin could provide a beneficial option for diabetes-related salivary hypofunction.