Abstract: Objective To investigate the clinical efficacy and safety of Ruyi Zhenbao Pill combined with transcutaneous electrical acupoint stimulation (TEAS) in the treatment of patients with postpartum lumbosacral pain. Methods A single-blind, randomized controlled trial was conducted. A total of 150 patients with postpartum lumbosacral pain admitted to Wenzhou People's Hospital between September 2021 and May 2023 were selected and randomly assigned, using a random number table, to either the intervention group or the control group, with 75 cases in each group. Both groups received a conventional intervention. The control group additionally received TEAS, while the intervention group received oral Ruyi Zhenbao Pill in addition to the control group's treatment. Visual analogue scale (VAS) score, Oswestry disability index (ODI) score, and serum levels of neuropeptide Y (NPY), substance P (SP), and prostaglandin E2 (PGE2) were compared between the two groups, as were efficacy and safety. Results After 1 and 2 weeks of treatment, the intervention group showed lower VAS and ODI scores, and lower serum SP and PGE2 levels, but higher NPY levels compared to the control group (P＜0.05). Over time, both groups showed decreasing trends in VAS and ODI scores and in serum SP and PGE2 levels, and an increasing trend in NPY levels (P＜0.05). The total effective rate was higher in the intervention group than in the control group (P＜0.05). No significant adverse reactions were observed in either group. Conclusion Ruyi Zhenbao Pill combined with TEAS can alleviate pain in patients with postpartum lumbosacral pain. The mechanism may be related to the upregulation of NPY expression and downregulation of SP and PGE2 expression. This combination therapy demonstrates significant efficacy and a favorable safety profile.