Objective The purpose of the present study was to assess the influence of type 2 diabetes mellitus (DM) on the evolution of pulpal and periapical pathology. Method and materials Two reviewers independently conducted a systematic search for articles published between 1 January 2001 and 31 December 2018 on MEDLINE/PubMed, ISI Web of Science, and Scopus databases. An additional manual search was also carried out. Results Ten studies fulfilling the inclusion criteria were included in the review (two longitudinal studies with 1-year follow-up comparing the success of primary root canal treatment between type 2 diabetic patients and non-diabetic patients, and eight cross-sectional studies). Analysis of the ten studies showed that inadequate control of type 2 DM may predispose and influence the inflammatory pulpal and periapical disease evolution. Conclusions The present systematic review suggests that there are biologic bases to suggest that type 2 DM may act as a risk factor for developing an endodontic pathology, affecting the course of the disease in terms of susceptibility, prevalence, progression, and tissue healing capacity as a consequence of a disrupted immune response. However, more well-designed clinical investigations carrying out suitable research methodologies are needed to elucidate the influence of type 2 DM on the pulpal and periapical disease evolution.