To investigate whether the use of different species of Sargassum is related to antagonistic medicament, we proposed the present study to systematically evaluate antigoitrous effect (FT3, FT4, thyroid weight, and histological changes) and toxicity (liver/renal function parameters) and to clarify the potential underlying mechanism (TSH, TRH, Tg mRNA, and TPO mRNA) of the two different species of Sargassum in HYD (HYDf and HYDp) in PTU-reduced goiter rats. Here, TPO is linked to goiter.