Aims To evaluate the efficacy and safety of PuraStat®, a self-assembling peptide hemostatic agent, for oozing-type hemorrhage after thyroidectomy, particularly in anatomically challenging areas where conventional hemostasis may risk recurrent laryngeal nerve injury. Methods This is a single-center, single-arm, prospective exploratory interventional study. Patients aged ≥18 years with ECOG performance status 0–1 undergoing anatomical thyroidectomy via conventional and endoscopic approaches were enrolled. When oozing-type hemorrhage (bleeding activity grade 1–3) persisted after thyroid transection and was difficult to control using standard ligation or cauterization, PuraStat® was applied. The primary endpoint was the proportion of cases requiring additional hemostatic procedures. Secondary endpoints included time to hemostasis, total hemostatic time, intraoperative additional hemostatic interventions, preparation time, amount of PuraStat® used, postoperative outcomes, and adverse events within 90 days. Results Patient enrollment is ongoing. Preliminary observations suggest that PuraStat® provides effective and feasible hemostasis in selected cases, including minimally invasive approaches such as endoscopic thyroidectomy. Its use appears particularly advantageous in anatomically constrained areas adjacent to the recurrent laryngeal nerve where conventional ligation or cauterization may be technically challenging. No major safety concerns have been identified to date. Detailed quantitative analyses are ongoing. Conclusion PuraStat® may represent a useful adjunct for hemostasis in thyroid surgery, especially in situations where conventional techniques carry a potential risk of thermal or mechanical injury to the recurrent laryngeal nerve. This approach may help expand safe hemostatic options, although further validation with complete data is required.