Background: Telemedicine and e-health services are crucial tools to help patients undergo complex treatments, such as radioactive iodine treatment (RIT), during the COVID-19 pandemic. However, the efficacy of such tools in real-life practice in Thailand is unknown. Objective: To investigate the usability, acceptability, and user needs for the Love Thyroid application and book among patients with hyperthyroidism. Methods: A descriptive study, 120 patients with hyperthyroidism who received RIT were given the chance to use both the Love Thyroid application and book. Then, all patients completed the electronic questionnaire that gathers information, including the usability, acceptability and user needs for both media. Results: The Love Thyroid application was more helpful in following patients up after RIT and has a more attractive design than the book (P < .05). The book was easier to search for information than the application (P < .05). Furthermore, the application had higher acceptability than the book in terms of the confidence in data security, ease of handling, and satisfaction (P < .05). The usefulness of the educational contents was comparable for both media. The application was more likely to be recommended by the patients to others than the book (P < .05). Conclusions: Mobile applications, such as the Love Thyroid application, had good usability and acceptability as informative tools for patients with hyperthyroidism underwent RIT.