To investigate the effects of levothyroxine combined with methimazole on the clinical efficacy of hyperthyroidism treatment. A total of 102 patients with hyperthyroidism admitted to our hospital from January 2018 to June 2020 were selected and randomly assigned into the combination group (levothyroxine combined with methimazole) and the control group (methimazole treatment alone). 3 months after treatment, the two groups were compared with regard to clinical efficacy, changes in ultrasound findings, the thyroid hormones, and serum indexes and the adverse reactions rate. The combination group (98.04%) outperformed the control group (86.27%) in total effective rate, and the overall efficacy garnered the similar result. After treatment, the combination group showed advantages in thyroid hormone level, serum index level, thyroid volume, superior thyroid artery diameter, and maximum blood flow rate when compared with those of the control group (P<0.05). As for the adverse reactions rate, the combination group was superior to the control group (3.92%vs15.69%) (P<0.05). Levothyroxine combined with methimazole promotes the clinical efficacy of hyperthyroidism treating, reduces thyroid volume and the diameter of superior thyroid artery, enhances the patient's thyroid function and serum index, with higher safety profile.