Irrigating solutions play an important role in the eradication of intracanal microbes and debris dissolution during endodontic treatment. Different combinations of solutions and protocols have been advocated, with sodium hypochlorite (NaOCl), ethylenediamine tetra acetic acid (EDTA), and chlorhexidine (CHX) remaining the most widely used ones by many clinicians. Although these solutions provide efficient inorganic dissolution and antimicrobial capacity, their use has also been reported to cause undesired effects on root dentin composition and mechanical and biomechanical properties, such as microhardness, surface roughness, bond strength, and matrix metalloproteinase (MMP) activity. Several corroborating studies attribute these changes in mechanical properties of dentine to the use of irrigating solutions, and there are limited reports on how the solutions affect the expression of MMPs, which may be a correlating link to understanding the role of these enzymes in dentin collagen and changes in the mechanical properties of dentin. Hence, using the basis of several studies from the literature, the objective is to comprehensively review the influence of individual and combined irrigating solutions on root dentine structure and the activity of the MMPs.