Background: This study aimed to evaluate whether dexmedetomidine (DEX) can relieve postoperative pain and reduce stress reaction after laparoscopic uterine fibroids (UF) surgery. Methods: This randomized controlled study included 100 patients age range of 40–60 years, American Society of Anesthesiologists (ASA) 1–2 grade, admitted for laparoscopic UF surgery from January 2020 to October 2023. The patients were randomly allocated to the DEX group (n = 50) and non-DEX group (n = 50). The visual analogue scale (VAS), Richmond Agitation-Sedation Scale (RASS) score, anesthesia time, spontaneous breathing recovery time, consciousness recovery time, extubation time, and recovery room time were recorded. Results: The VAS of the DEX group was smaller than that of the non-DEX group at half an hour, but there was no significant difference in VAS at 1 h, 12 h and 24 h. Dex group has a RASS value closer to zero than non-DEX group at half an hour. There was no significant difference in RASS at 1 h, 12 h, or 24 h. There were differences in spontaneous breathing recovery time, consciousness recovery time, extubation time, recovery room time, chills and nausea between the two groups. Conclusion: Application of DEX in perioperative period can relieve postoperative pain, reduce stress reaction after laparoscopic UF surgery. Clinical Trial Registration: The study has been registered on https://classic.clinicaltrials.gov/ (registration number: NCT03524950).