Regenerative endodontic procedures (REPs) offer an alternative to apexification in necrotic immature permanent teeth, promoting continued root development and dentinal wall thickening. Success in REPs requires effective disinfection and the survival of dental-derived mesenchymal stem cells (DMSCs), such as dental pulp stem cells (DPSCs), stem cells from the apical papilla (SCAPs), and periodontal ligament stem cells (PDLSCs). This review investigates the biocompatibility of irrigation solutions, including sodium hypochlorite (NaOCl), ethylenediaminetetraacetic acid (EDTA), and chlorhexidine (CHX), on DMSCs. Following PRISMA guidelines, a comprehensive search was conducted in PubMed, Scopus, Web of Science, Cochrane, and SciELO, with the last update on March 4, 2024. Studies from January 2008 to April 2024 assessing viability, proliferation, migration, differentiation, and mineralization of DMSCs treated with NaOCl, EDTA, and CHX were included. The papers were selected using PICOS criteria and quality was assessed using the PRILE checklist and risk of bias with the Quality Assessment Tool for In Vitro Studies. Of 738 studies identified, 15 met inclusion criteria. The findings suggest that NaOCl and CHX exhibit lower biocompatibility towards DMSCs compared to EDTA. NaOCl and CHX are cytotoxic to DMSCs, while EDTA demonstrates favorable biocompatibility, promoting osteogenic differentiation and mineralization. This highlights potential implications for irrigant selection in regenerative procedures, as appropriate irrigants may enhance cellular survival and improve clinical outcomes.