Purpose: To compare the antibacterial activities of two dentin bonding systems (DBS), Clearfil Protect Bond and Xeno III, by agar well, paper and dentin disks, and a cavity tooth model. Materials and Methods: For the well technique, the test materials were filled in the agar wells inoculated with Streptococcus mutans (ATCC 25175). The paper disks were embedded in adhesives and placed on the seeded agar plates for the second technique. The adhesives were applied on the dentin disks and placed in holes in the plates for the third technique. After 48 h, the zones of inhibition were measured. In the cavity tooth model test, 3 cavities were prepared in the flat occlusal dentin of extracted human molars. The teeth were left in S. mutans for 72 h to allow bacterial invasion. The DBS were applied in the same manner as in clinical application on each of the two infected cavities and the third was left unapplied for control. The teeth were kept in saline for 72 h. Standard amounts of dentin chips were obtained from the cavity walls and the number of bacteria recovered was counted. Results: The results were analyzed by factorial ANOVA and Dunnett C test. Clearfil Protect Bond primer exhibited the greatest inhibition zones followed by Consepsis and unpolymerized Xeno III in all the techniques tested (p = 0.05). Clearfil Protect Bond resulted in significantly less bacterial recovery than Xeno III by the tooth cavity method (p = 0.05). Conclusion: Clearfil Protect Bond was found to be the most antibacterial material with all the techniques used. Furthermore, Clearfil Protect Bond was able to inactivate the bacteria in the cavity more effectively than Xeno III. Keywords: antibacterial activity, adhesive system, MDPB