Iodine-containing antiseptics and contrast agents used in neonates can lead to hypothyroidism, which, although often transient, may require prolonged treatment in some cases. Untreated hypothyroidism, even if temporary, can negatively impact neurodevelopment, particularly in preterm infants. In addition, gastrointestinal disorders such as short bowel syndrome or ileus may hinder oral levothyroxine absorption, necessitating alternative administration routes. Here, we present a late preterm neonate who developed hypothyroidism after iodine-containing contrast agent use for diagnosing total intestinal aganglionosis. The patient failed to respond to oral and rectal levothyroxine administration due to functional ileus and persistent gastrointestinal drainage. Subsequently, levothyroxine was administered via the buccal route by diluting the tablet form. The treatment resulted in rapid normalization of thyroid function tests, with no adverse effects observed. In our case, buccal administration of diluted levothyroxine tablets was found to be a beneficial treatment approach for managing hypothyroidism in a patient unable to tolerate oral therapy due to intestinal dysmotility and malabsorption, particularly in the absence of alternative formulations. Furthermore, it highlights the importance of monitoring thyroid function in neonates exposed to iodine-containing agents, especially those with gastrointestinal motility disorders. Buccal levothyroxine may provide a practical solution for managing hypothyroidism in similar clinical scenarios.