INTRODUCTION: The purpose of this systematic review and network meta-analysis was to evaluate the efficacy and safety of different preemptive analgesia measures given before laparoscopic cholecystectomy (LC) for postoperative pain in patients. METHODS: We conducted a comprehensive search in databases including PubMed, Web of Science, Embase, and the Cochrane Library up to March 2024, and collected relevant research data on the 26 preemptive analgesia measures defined in this article in LC surgery. Outcomes included postoperative Visual Analogue Scores (VAS) at different times (2, 6, 12, and 24 h), opioid consumption within 24 h post-operation, time to first rescue analgesia, incidence of postoperative nausea and vomiting (PONV), and incidence of postoperative headache or dizziness. RESULTS: Forty-nine articles involving 5987 patients were included. The network meta-analysis revealed that multimodal analgesia, nerve blocks, pregabalin, and gabapentin significantly reduced postoperative pain scores at all postoperative time points and postoperative opioid consumption compared to placebo. Tramadol, pregabalin, and gabapentin significantly extended the time to first rescue analgesia. Ibuprofen was the best intervention for reducing PONV incidence. Tramadol significantly reduced the incidence of postoperative headache or dizziness. Subgroup analysis of different doses of pregabalin and gabapentin showed that compared to placebo, pregabalin (300 mg, 150 mg) and gabapentin (600 mg, 300 mg, and 20 mg/kg) were all more effective without significant differences in efficacy between these doses. Higher doses increased the incidence of PONV and postoperative headache and dizziness, with gabapentin 300 mg having a lower adverse drug reaction (ADR) incidence. CONCLUSIONS: Preemptive analgesia significantly reduced postoperative pain intensity, opioid consumption, extended the time to first rescue analgesia, and decreased the incidence of PONV and postoperative headache and dizziness. Multimodal analgesia, nerve blocks, pregabalin, and gabapentin all showed good efficacy. Gabapentin 300 mg given preoperatively significantly reduced postoperative pain and ADR incidence, recommended for preemptive analgesia in LC. TRIAL REGISTRATION: PROSPERO CRD42024522185.