Endodontic-periodontal lesions (endo-perio) are clinically intricate conditions involving the dental pulp and associated periodontal tissues' infection or inflammation. These lesions are difficult to diagnose and treat because of their mixed origin, shared microbiological factors, anatomical considerations, and, in some cases, superimposed varying stages of disease. This systematic review sought to evaluate recent in vitro studies (2018 – 2025) on treating endo-perio lesions, emphasizing assessment related to antimicrobial action, biofilm disintegration, cytotoxicity, apoptosis, mineralization, and inflammatory response. Following PRISMA 2020 criteria, scoped searches were conducted in PubMed and Scopus. Inclusion criteria consisted of peer-reviewed in vitro studies published in English that focused on managing endodontic-periodontal lesions using medicaments, irrigation systems, photodynamic therapy, or bioceramic sealers. Quantitative data about experimental designs, including relevant measures about outcomes alongside metrics such as calculation results from statistical tests, were collected. Customized criteria created especially for controlled environments were used to quantify the danger of bias. Nine studies were included. Because of its low cytotoxicity profile and prolonged ion release, calcium hydroxide demonstrated notable antibacterial efficacy against E. faecalis and P. gingivalis, especially when combined with chlorhexidine. The SWEEPS, PIPS, and EDDY laser-activated irrigation systems significantly surpassed both conventional and ultrasonic systems in removing multispecies biofilms within grooves and dentinal tubules. Photodynamic therapy employing curcumin or phycocyanin also exhibited notable reductions in bacterial counts. In vitro, research indicates integrated strategies employing enhanced irrigation techniques alongside biocompatible sealers and antimicrobial compounds show promise in treating endo-perio lesions. Furthermore, issues of dose-dependent cytotoxicity and inflammatory response warrant further examination.
