Background: Transoral endoscopic thyroidectomy has been gaining popularity as it allows patients to avoid a visible scar in the neck. However, there are still exiting disadvantages of traditional transoral endoscopic thyroidectomy,including numbness in the lower jaw or excessive edema. Therefore, we designed and applied a novel Mini transoral endoscopic thyroidectomy on patients requiring for thyroidectomy.Patients and Methods: A total of 55 patients requiring for unilateral thyroidectomy who underwent novel Mini transoral endoscopic thyroidectomy (Mini group) were identified from August 2019 to December 2019. As a comparison, a matched cohort of 55 patients requiring for conventional transoral endoscopic thyroidectomy was also identified. The two groups were analyzed in terms of clinical characteristics, perioperative/operative clinical date and post-operative complications. Results: The hospitalization time of patients in the Mini group was obviously less than that in traditional group. Furthermore, the numbness of the lower jaw, nylon wire examination score, pressure needle puncture examination score, or numbness VAS score indicated that the degree of numbness of the jaw in Mini group is significantly better than the traditional group. Moreover, the pain of the axillary incision using the pain VAS score method also showed that Mini group is significantly better than the traditional group. The results of pain of the axillary incision using the VAS score method also showed that novel Mini group was significantly better than that in the traditional group. Furthermore, dysfunction of mandibular muscles was observed in six of fifty-five patients in the traditional group, whereas no dysfunction of mandibular muscles observed in Mini group. At last, the degree of postoperative mandibular edema in Mini group was markedly slighter than that in traditional group. The post-operation infection rate was markedly lower in Mini group.Conclusion: The new novel Mini transoral endoscopic thyroidectomy is safe and feasible, and reduces the damage to the functional muscles such as the mandibular diaphragm and lower lip muscles, which significantly reduces the numbness and edema of the mandible after surgery. Our novel Mini transoral endoscopic thyroidectomy is a feasible and safe advancement, which can be a viable alternative protecting patients from insufferable numbness and pain.