Excessive exposure of iodine over a time is well known to cause thyroid dysfunction, which may be followed by different effects on body organs. The present study aimed to illustrate the impacts of exposure of rats to excess iodine (above the tolerable range) and the reversibility of any negative impacts on hormonal profile related to thyroid besides cortisol and the hematological and biochemical parameters along with the histopathological alterations in the thyroid gland, liver, kidneys, and heart. Seventy-five rats were divided equally into three groups: Group 1 was control animals. Groups 2 and 3 received sodium iodide (NaI) orally at a dose of (35 and 70 mg/kg BW), which corresponded to (500 and 1000) times excess iodine from the physiological dose, respectively for 30 days, then the NaI administration stopped in the treated groups for 15 consecutive days. Blood and tissue samples were collected twice for various experimental tests after 30 and 15 days of exposure to excess iodine and stopping the exposure, respectively. Overall results revealed that excess iodine in both tested groups developed a hyperthyroid condition, hypercortisolism, relative polycythemia, neutropenia, elevation in serum liver and cardiac enzymes activities, hyperprotenemia, hyperglobulinemia, elevation in serum urea, and cardiac troponin I concentrations (p < 0.05). It was concluded that the excess iodine caused hyperthyroidism, which was associated with significant changes in erythrogram and leukogram and alterations in hepatic, renal, and cardiac functions in an iodine dose-dependent damage relationship and the most of negative impacts continued after stopping the administration.