Background: Povidone-iodine (PVP-I) is an antiseptic that is commonly used as an alternative to alcohol in clinical settings, including for perioperative skin disinfection. However, the presence of iodine in PVP-I can result it adverse effects on thyroid function. This study explored the effect of PVP-I on thyroid function and assessed its safety profile.Methods: We assessed thyroid function in patients before and after treatment with Repigel (topical liposomal hydrogel with 3% PVP-I) between January 2017 and January 2023, for a period of at least 2 weeks. Patients were stratified by age, sex, and previous history.Results: No significant changes in thyroid function were observed in the 61 patients enrolled until 2 weeks after application of Repigel. Significant increases in T3, T4, and free T4 levels were detected 4 weeks after Repigel application. A comparison of the initial thyroid function test (TFT) and TFT 4 weeks post-application found that the mean T3 levels were 71.12 ± 17.55 ng/dL and 59.84 ± 18.60 ng/dL and mean T4 levels were 6.48 ± 1.49 µg/dL and 5.50 ± 1.36 µg/dL, respectively. The mean free T4 levels were 1.08 ± 0.39 ng/dL and 0.90 ± 0.19 ng/dL, respectively.Conclusion: Changes in thyroid function during the application of Repigel were observed. We conclude that thyroid function should be examined at regular intervals before and after topical application of Repigel. Additionally, clinicians should exercise caution when administering iodine-containing substances such as Repigel to patients with abnormal thyroid function, and schedule follow-up TFTs at 4 weeks.