Radioiodine (RI) treatment is widely used in patients with differentiated thyroid cancer. However, RI exposure often induces salivary gland (SG) dysfunction. In this study, we investigated the effect of curcumin on RI-induced SG dysfunction in mice.Mice were assigned to one of four groups (n = 6 per group) as follows: normal control, RI only, RI + curcumin, and RI + amifostine group. Salivary flow rate, lag time, and changes in 99m Tc (technetium)-pertechnetate uptake and excretion were measured, and changes in SG morphology and histology were analysed. Salivary epidermal growth factor content, amylase, and superoxide dismutase (SOD) activities were also measured. A terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was performed to assess SG apoptosis, and the expression of apoptosis-related protein was determined by western blotting. The reduced salivary flow rate and prolonged lag time in the RI group was restored by treatment with curcumin or amifostine. In the histological analysis, compared with the RI group, RI + curcumin and RI + amifostine groups had more mucin-rich acini and less periductal fibrosis.Compared with the RI group, RI + curcumin and RI + amifostine groups showed evidence of tissue remodelling, with a greater number of salivary epithelial cells (AQP-5-positive), SG ductal cells (CK18-positive), endothelial cells (CD31-positive), and myoepithelial cells (α-SMA-positive). RI + curcumin and RI + amifostine groups alleviated RI-induced cell death, demonstrating antiapoptotic effect, compared with the RI group. Both SOD activity and the protein expression levels of SOD2 were higher in the RI + curcumin and RI + amifostine groups than in the RI group. Our results demonstrate that curcumin ameliorates RI-induced SG dysfunction in mice.