Introduction: Foraminal Enlargement (FE) is a cleaning performed in the apical-most region of the tooth, in order to optimize root disINFECTION. This systematic review evaluated the influence of FE during root canal treatment on bacterial reduction and repair of the PERIAPICAL lesion. Materials and Methods: Searches in PubMed/MEDLINE, Scopus, Cochrane Library, Web of Science, Embase, Scielo, Lilacs and OpenGrey were performed until January-2024. Ex vivo and in vivo studies evaluating the effects of FE in the bacterial reduction and repair of the PERIAPICAL lesion were included, respectively, followed by risk of bias assessment (modified version of Joanna Briggs Institute’s for ex vivo studies and Systematic Review Centre for Laboratory animal Experimentation’s risk of bias tools for in vivo studies). The meta-analysis was not feasible and a qualitative summary for each outcome was provided. Results: Of 950 studies, 2 in vivo studies were eligible, using animal models with infected TEETH. Of these two, PERIAPICAL repair was evaluated with hematoxylin-eosin stain, and FE improved PERIAPICAL healing. Regarding ex vivo studies, 3 were eligible, using extracted human TEETH. The inoculations in ex vivo models were performed with Enterococcus (E. ) faecalis, and FE reduced E. faecalis in the ex vivo models. Conclusions: Foraminal enlargement seems to increase bacterial reduction within the root canal, and provide major PERIAPICAL tissue repair on the histological analysis in animal studies. However, caution is necessary when translating these results to the clinical environment.