Objective To explore the therapeutic effect of ultrasound-guided microwave ablation in patients with benign thyroid nodules and its impact on thyroid related hormones. Methods A total of 200 patients with benign thyroid nodules admitted from January 2020 to January 2023 were selected as study subjects. They were divided into two groups by random number table method, with 100 patients in each group. The control group received open surgery treatment, while the observation group received ultrasound-guided microwave ablation treatment. Treatment outcomes were evaluated in both groups, including surgical indicators, preoperative and postoperative 7 d inflammatory factors and thyroid related hormones, and incidence of postoperative complications and recurrence. Results The observation group had lower surgery time, hospital stay, intraoperative bleeding volumn, and hospitalization costs than the control group （P<0.05）. Both groups had varying degrees of inflammatory reactions 7 d after surgery, but the observation group showed lower levels of hypersensitive C-reactive protein （hs-CRP）, tumor necrosis factor-alpha （TNF-α）, epinephrine （E）, and norepinephrine （NE） than the control group （P<0.05）. Both groups had elevated levels of thyroid related hormones 7 d after surgery, but the levels of thyroid stimulating hormone （TSH）, serum free triiodothyronine （FT₃）, and serum free thyroxine （FT₄） in the observation group were lower than those in the control group （P<0.05）. The incidence rates of surgical complications, postoperative residuals, postoperative scars, and recurrence in the observation group were 2.00%, 2.00%, 1.00%, and 2.00%, respectively, which were lower than those in the control group （10.00%, 8.00%, 6.00%, and 8.00%, respectively） （P<0.05）. Conclusion Ultrasound-mediated microwave ablation is effective in treating patients with benign thyroid nodules, has advantages in reducing surgical trauma and postoperative complications, and has little impact on thyroid hormones and inflammatory factors, which is worth promoting and applying.