Resveratrol (Res), found abundant in many medicinal plants, exerts multiple biological functions in the body, including anti-inflammatory, antioxidant, and anti-aging properties. Xerostomia is a major symptom of salivary gland dysfunction in menopausal women, which significantly compromises the quality of life. Here, we investigated the effect of Res on estrogen deficiency-induced salivary gland dysfunction in rats. We found that Res administration could reduce body weight and water consumption, and increase salivary fluid secretion and blood flow of the submandibular gland. Furthermore, Res therapy alleviated histological lesions, increased AQP5 expression, and inhibited cell apoptosis in sub -mandibular gland tissue. Meanwhile, the action of antioxidants was restored and the levels of inflam-matory cytokines were attenuated by Res supplementation. Collectively, Res effectively improved estrogen deficiency-induced hyposalivation, which may provide a novel, safe, and practical approach to protect the salivary glands of estrogen-deficient females against xerostomia.(c) 2022 Elsevier Inc. All rights reserved.