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Cavity disinfection becomes an important step before a dental restorative procedure. The disinfection can be obtained cleaning the dental cavity with antimicrobial agents before the use of adhesive systems. The aim of this study was to conduct a systematic review on the effect of different cavity disinfectants on restorations’ adhesion and clinical success. A search was carried out through the Cochrane Library, PubMed, and Web of Science. In vitro and in situ studies reporting results on dentin bond strength tests, and clinical studies published until August 2020, in English, Spanish and Portuguese were included. The methodological quality assessment of the clinical studies was carried out using the Revised Cochrane risk-of-bias tool. Chlorhexidine could preserve adhesion to dentin. EDTA and ethanol had positive results that should be further confirmed. Given the significant lack of scientific evidence, the use of lasers, fluoridated agents, sodium hypochlorite, or other products as cavity disinfectants should be avoided. Chlorhexidine is a safe option for cavity disinfection with adequate preservation of adhesion to dentin. Moreover, future researches should be focused on the efficacy of these disinfectants against cariogenic bacteria and their best application methods.