Different surface preparation and treatment methods may have dissimilar effects on the microleakage of composite resin. This study was conducted to determine the deproteinizing effect of 10% bromelain enzyme, 10% papain enzyme, CO2 , and erbium-YAG laser in regard to decrease in the microleakage of composite restorations. Thirty teeth were selected and 60 class V cavities were prepared on the lingual and buccal sides. They were divided into six groups (n = 10): Group 1, phosphoric acid gel; Group 2, bromelain enzyme 10%; Group 3, papain enzyme 10%; Group 4, mixed papain and bromelain enzymes 10%; Group 5, CO2 laser; and Group 6, erbium-YAG laser. They were stored in basic fuchsine and dye penetration was evaluated. Kruskal-Wallis and Mann-Whitney tests were used for statistical analysis, p < 0.05 RESULTS: In both occlusal and gingival margins, comparison of microleakage between groups 1, 2, 3, 4, and 5 showed no significant differences (p = 1) and group 6 had a significant difference with other groups (p ˂ 0.001). Microleakage of composite resin in the dentin surface was not affected significantly using either bromelain or papain 10% enzymes or erbium laser. However, CO2 laser had a negative effect on the enamel and dentin margins and increased the microleakage. Erbium laser showed a better effect than enzymes on microleakage.