The objective of the study was to review the literature on root anatomy and canal configuration in permanent mandibular second molar based on Vertucci classification. Online electronic databases such as PubMed-Medline, Embase, Scopus, and Cochrane Library were searched using appropriate keywords from the earliest available date till 10 th February 2021 restriction on language. Additional sources such as Google Scholar, major journals, unpublished studies, conference proceedings, and cross-references were explored. Information curated for data extraction included methodology, population, sample size (number of teeth), number of root canals, and type of root canal configuration (RCC). Thirty-seven articles were selected with a total of 12,393 permanent mandibular second molar teeth. In the mesial root, Type IV canal configuration with 37.3% was more frequent, having two canals with 70.4%. In the distal roots, one canal was more prevalent with 77% occurrence, and Type I canal configuration was more frequent with 85.2%. Comprehensive knowledge of tooth anatomy and root canal morphology is crucial to root canal treatment. Therefore, an understanding of the canal configuration and anatomy is necessary for the dentist to enhance successful endodontic treatment. Our systematic review findings reveal a wide variety of possible canal configurations among permanent mandibular second molar, while the number of canals ranged from 1 to 5 in number. The evidence is intended to help dental practitioners to avoid mishaps such as perforation and missing canals and anticipation of potential complications during treatment.