The present study aimed to evaluate the efficiency, effectiveness, and biocompatibility of two agents used for the chemomechanical removal of carious dentin. Sixty extracted carious human teeth were treated with a conventional bur (CBG) or chemomechanical agents - Papacarie Duo (PG) and Brix 3000 (BG). Treatment efficiency and effectiveness were assessed by the working time for carious dentin removal and Knoop microhardness values, respectively. Human pulp fibroblasts (FP6) were used to evaluate cytotoxicity by incorporating MTT dye, and genotoxicity was evaluated with the micronuclei test. The carious tissue was removed in a shorter time with CBG (median = 54.0 seconds) than the time required for chemomechanical agents (p = 0.0001). However, the time was shorter for Brix 3000 (BG) than that for Papacarie Duo (PG), showing mean values of 85.0 and 110.5 seconds, respectively. Regarding microhardness testing, all approaches tested were effective (p < 0.05). The final mean microhardness values were 48.54 ± 16.31 KHN, 43.23 ± 13.26 KHN, and 47.63 ± 22.40 KHN for PG, BG, and CBG, respectively. PG decreased cell viability compared to that of BG, but it presented no genotoxicity. Brix 3000 may be a good option for chemomechanical dentin caries removal due to its reduced removal time and lower cytotoxicity compared to the other treatment options.