Background Understanding of changes in salivary and lachrymal gland functions after radioiodine therapy (131I-therapy) remains limited; and, to-date no studies have evaluated dose-response relationships between absorbed dose from 131I-therapy and dysfunctions of these glands. This study investigates salivary/lachrymal dysfunctions in differentiated thyroid cancer (DTC) patients six months after 131I-therapy, identifies 131I-therapy related risk factors for salivary/lachrymal dysfunctions, and assesses the relationships between 131I-therapy radiation dose and these dysfunctions. Methods A study was conducted involving 136 DTC patients treated by 131I-therapy of whom 44 and 92 patients received 1.1 and 3.7 GBq, respectively. Absorbed dose to the salivary glands was estimated using a dosimetric reconstruction method based on thermoluminescent dosimeters measurements. Salivary and lachrymal functions were assessed at baseline (T0, i.e., immediately prior to 131I-therapy), and 6 months later (T6) using validated questionnaires and salivary samplings, with and without stimulation of the salivary glands. Statistical analyses included descriptive analyses and random-effects multivariate logistic and linear regressions. Results There was no difference between T0 and T6 in the level of parotid gland pain, nor was there difference in the number of patients with hyposalivation, but there were significantly more patients with dry mouth sensation and dry eyes after therapy compared to baseline. Age, menopause, depression and anxiety symptoms, history of systemic disease, and not taking painkillers in the last 3 months were found to be significantly associated with salivary or lachrymal disorders. Significant associations were found between 131I-exposure and salivary disorders adjusted on the previous variables: e.g. per 1-Gy increase in mean dose to the salivary glands, OR=1.43 (95%CI 1.02-2.04) for dry mouth sensation, ß=-0.08 (95%CI -0.12;-0.02) mL/min for stimulated saliva flow, and ß= 1.07 (95%CI 0.42;1.71) mmol/L for salivary potassium concentration. Conclusions This study brings new knowledge on the relationship between the absorbed dose to the salivary glands from 131I-therapy and salivary/lachrymal dysfunctions in DTC patients 6 months after 131I-therapy. Despite the findings of some dysfunctions, the results do not show any obvious clinical disorders after the 131I-therapy. Nevertheless, by identifying risk factors, this study encourages clinicians to adapt the therapy for patients at risk of salivary/lachrymal complications.