INTRODUCTION: Third molar surgery often results in inflammatory complications, such as pain, trismus, and swelling. This study aims to evaluate the effectiveness and safety of various interventions in alleviating postoperative inflammatory complications after third molar surgery. METHODS: A systematic review of PubMed, Ovid and Scopus databases identified randomised controlled trials (RCTs) assessing interventions used to alleviate postoperative inflammatory complications after third molar surgery. The primary outcome was pain measured by visual analogue score (VAS). Interventions were ranked using Surface Under Cumulative Ranking (SUCRA). RESULTS: Analysis of 77 RCTs evaluated intervention efficacy for pain, trismus and swelling. Antimicrobial photodynamic therapy (aPDT) combined with photobiomodulation (PBMT) was ranked as most effective in reducing pain at day three post-surgery (SMD -4.8, SUCRA 95.9%. Betamethasone (BET), ibuprofen (IBU) and paracetamol (PCM) showed similar efficacy by day seven (SMD: -5.66, SUCRA 92.4%, 89.6%, and 88.1% respectively). PBMT and ozone therapy (OT) significantly reduced trismus on day three (PBMT: SMD -5.02, OT: SMD -3.26, both p < 0.05). Oxaprozin (OXA), OT, dexamethasone (DEX) and PBMT were significantly effective by day seven (OXA: SMD -4.4, OT: SMD -2.42, DEX: SMD -1.53, PBMT: SMD 0.008). Diclofenac (DIC) was effective for swelling on day two (SMD -3.22), while OXA was effective on day seven (SMD -4.53). Regarding safety, only 14 studies reported side effects, with 10 of them reporting no adverse events. The most documented adverse events were with piroxicam and ketorolac. CONCLUSION: Antimicrobial photodynamic therapy combined with photobiomodulation was identified as the most effective intervention for alleviating postoperative pain after third molar surgery. PBMT consistently demonstrated statistical significance in its efficacy for pain, trismus and swelling on all evaluation days, but with varying ranks. Since the safety data were limited in all studies, highlighting the need for further research on potential adverse events. Keywords: third-molar surgery, postoperative inflammatory complications, pain, trismus, swelling, oedema, network meta-analysis.