The purpose of this systematic review was to compare the efficacy and efficiency of chemical-mechanical agents (CMA) versus rotary systems (RS) for the removal of dental caries (DC) in permanent molars. The search was carried out in five electronic databases (PubMed, Ebsco, Scopus, ScienceDirect, LILACS) and gray literature, complemented with a manual search in impact journals until July 2022 in English, Spanish and Portuguese. The efficacy of DC treatment was analyzed histologically, microbiologically, radiographically, or physicochemical-mechanically and efficiency was evaluated according to the shortest time for removal. Risk of bias was assessed with the RoB tool. Nine studies were included out of 914 publications that evaluated 337 molars with split design treated with low- or high-speed RS and CMA, such as Carisolv, Papacarie, Carie Care and Brix 3000. Significant differences were found among the studies (p<0.05), with Carisolv presenting a higher amount of residual caries, the presence of bacteria in dentin and less extent or volume of extracted caries, while Papacarie showed an absence of smear in dentin tubules and RS obtained higher microhardness values and required less time for removal. There was no difference between the two methods with respect to calcium-phosphorus titration or bond strength (p≥0.05). CMAs removed DC with less invasion to sound dentin tissues compared to RS, but reduced surface hardness and required a longer removal time.