Objective: To investigate the efficacy and safety of the treatment with Mailuoshutong pill and dalteparin on patients with hypoparathyroidism after total thyroidectomy. Methods: The clinical data of 1 145 patients with thyroid cancer after total thyroidectomy and lymph node dissection were collected and retrospective analyzed at Breast and Thyroid Surgery Department of Zibo Central Hospital from January 1, 2018 to April 1, 2021. There were 389 patients with hypoparathyroidism were involved, in which 305 patients (as an anticoagulation group) were treated with combination of Mailuoshutong pill and calcium supplement, and 84 patients (as a control group) were treated with calcium supplement. The incidence of hypoparathyroidism, recovery time, decannulation time, and average daily drainage volume between the 2 groups were analyzed. Results: The incidence of postoperative hypothyroidism in 1 145 patients was 33.97%. The rate of parathyroid injury in the anticoagulation group was lower than that in the control group (P<0.05). There was no significant difference in decannulation time (P=0.10) and average daily drainage volume (P=0.80) between the 2 groups. The recovery of the anticoagulation group was significantly better than the control group on the 15th, 30th, 90th, and 180th day after the operation (all P<0.05). Conclusion: Calcium supplement, Mailuoshutong pill, and dalteparin therapy for patients with hypoparathyroidism after total thyroidectomy can improve, the recovery of parathyroid function and reduce the incidence of permanent functional damage. It is safe and reliable for postoperative use.