The molecular fate of thyroglobulin (Tg) is controlled by oligomerization, a means of storing Tg at high concentrations, and deoligomerization. The oligomerization of bovine Tg are intermolecular reactions that occur through oxidative processes, such as disulfide and dityrosine formation, as well as isopeptide formation; disulfide formation is primarily responsible for Tg oligomerization. Here, the protein disulfide isomerase (PDI) and/or peroxidase-induced oligomerization of unfolded thyroglobulins, which were prepared by treating bovine Tg with heat, urea or thiol/urea, was investigated using SDS-PAGE analyses. In addition, the enzymatic oligomerization was compared with non-enzymatic oligomerization. The thermally-induced oilgomerization of Tg, dependent on glutathione redox state, was affected by the ionic strength or the presence of a surfactant. Meanwhile, PDI-catalyzed oligomerization, time and pH-dependent, was the most remarkable with unfolded/reduced Tg, which was prepared from a treatment with urea/DTT, while the thermally-unfolded Tg was less sensitive. Similarly, the oligomerization of unfolded/reduced Tg was also mediated by peroxidase. However, PDI showed no remarkable effect on the peroxidase-mediated oligomerization of either the unfolded or unfolded/reduced Tg. Additionally, the reductive deoligomerization of oligomeric Tg was exerted by PDI in an excessively reducing state. Based on these results, it is proposed that PDI catalyzes the oligomerization of Tg through the disulfide linkage and its deoligomerization in the molecular fate, and this process may require a specific molecular form of Tg, optimally unfolded/reduced, in a proper redox state.