The aim of this study was to determine whether there was a correlation between salivary symptoms and salivary functioning following radioiodine therapy. Fifteen patients receiving radioactive iodine therapy for differentiated thyroid cancer completed a questionnaire assessing their salivary and nasal symptoms and underwent salivary scanning prior to therapy and 3 and 12 months after therapy. Measures of salivary gland accumulation and secretion were correlated with scores of salivary and nasal symptomatology. The mean number of salivary, nasal, and total symptoms at 3 months increased significantly over the number of symptoms at baseline by 3.7, 2.7, and 6.3 symptoms respectively (p values 0.001, 0.0046, and <0.001). The mean right parotid gland accumulation and secretion of radioisotope declined significantly at 3 months, compared with baseline. There was no association between the increase in salivary, nasal, or total symptoms and the change in scintigraphy measures. The increases in nasal and total symptoms were significant in those with co-existent Hashimoto’s disease, compared with those without this condition (p values 0.01 and 0.04). Nasal symptoms decreased (p value 0.04) in those who used sour candies, compared with those who did not. Increasing body mass index was significantly associated with increasing nasal symptoms (p value 0.05). Greater decline in salivary parameters at 3 months compared with baseline was generally associated with heavier body weight, decreased thyroid cancer stage, absence of Hashimoto’s thyroiditis, and pre-menopausal status. Although salivary and nasal symptoms increased and salivary scintigraphy parameters decreased after radioiodine therapy, the variables associated with symptoms and changes in salivary scan parameters differed. A better understanding of the relationship between salivary gland symptoms and functioning, and the factors affecting susceptibility to salivary and nasal damage after radioiodine therapy is needed.