Objective <p>The management of endodontic-periodontal lesions involves both non-surgical and surgical approaches. However, the necessity of surgical interventions remains debated, with limited systematic evaluations of their effectiveness. This review aims to assess and synthesize current evidence on the strategies and prognosis of surgical treatments for endodontic-periodontal lesions, offering guidance for optimal surgical planning.</p> Materials and methods <p>A systematic review without meta-analysis (CRD42020165512) was conducted and reported using SWiM framework to analyze studies until January 2025. Electronic databases (MEDLINE, Embase, Web of Science) and reference lists were searched. Inclusion criteria targeted clinical studies (randomized trials or non-randomized cohort and case-control studies) that involved any kind of surgical interventions on patients with endodontic-periodontal lesions. The primary outcomes used to assess treatment efficacy were clinical attachment level, probing pocket depth and radiography findings. Risk of bias was assessed using the Cochrane RoB 2 and the ROBINS-I tools. The GRADE framework was used to assess the certainty of evidence.</p> Results <p>A total of 13 studies, including 6 randomized controlled trials and 7 non-randomized studies, were reviewed to evaluate non-surgical versus combined surgical and non-surgical approaches, timing of interventions, intraoperative materials, intracanal medicaments, single versus combined surgical techniques, and follow-up protocols. Surgical interventions combined with non-surgical treatment yielded better clinical outcomes than non-surgical treatment alone. Within surgical strategies, earlier intervention, use of platelet-rich fibrin (PRF) instead of resorbable collagen membrane, and intracanal medicament replacement appeared beneficial. However, titanium-prepared PRF showed no added advantage over PRF, and the combining multiple surgical types was not necessarily more effective. Most studies showed moderate to serious risk of bias, and the certainty of evidence was low to very low.</p> Conclusion <p>Current limited evidence suggests that surgical intervention may be beneficial in managing endodontic-periodontal lesions, particularly when preceded by non-surgical treatment.</p> Clinical relevance <p>Surgical treatment may help preserve teeth affected by endodontic-periodontal lesions, although current evidence shows highly individualized treatment strategies.</p>