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AbstractAims and Objectives:Matrix metalloproteinases (MMPs) cause degradation of the dentinal matrix, as they act actively on collagen fibrils, leading to their deterioration and collapse. MMP inhibitors are known to be used for the pre-treatment of human dentin before bonding. Most studies on the MMP inhibitors examined the effect of MMP inhibitors on bonding to sound dentin (SD), but few examine their effect on bonding to caries affected dentin (CAD). This systematic review aims to identify and summarize studies that have applied MMP inhibitors for pre-treatment of CAD, and examine the microtensile bond strength (µTBS), bond durability, and the mode of failure.Materials and Methods:A systematic review was performed using the PubMed database according to the PRISMA guidelines. A total of 785 original articles published between 2010 and 2022 were initially retrieved. Six studies were selected based on predefined inclusion-exclusion criteria, and their outcomes were extracted and analyzed. The methodological quality assessment was performed using a combined checklist that utilizes the reporting criteria mentioned in the checklist for reporting in-vitro studies guidelines and guidelines for reporting pre-clinical in vitro studies on dental materials.Results:All six studies included here showed a definitive increase of the µTBS when MMP inhibitors were applied to the CAD. The mode of failure was found to be predominantly adhesive in nature. The deviation in the values of µTBS was approximately 2-5 MPa on immediate and delayed testing.Conclusion:MMP-inhibiting agents could be considered for the pretreatment of teeth with CAD as a part of their tooth preparation area, thereby allowing the clinician to retain CAD and bond to the CAD without endangering the vital pulp.