Objective: to evaluate and compare the effect of different matrix metalloproteinases biodegradation inhibition protocols. Material and methods: 192 permanent molar sound teeth were collected. Using a diamond disk, wet grinding of the occlusal surface of all samples into flat surface to expose the superficial dentinal surface. 37% phosphoric acid was applied for 15 seconds, cleaned with water and dried with cotton rolls. Then, the molar teeth were divided into four main groups (n=48); group I; No treatment (control group), group II; Chlorhexidine (2%); group III; Minocycline (2%); group IV; Sodium Hypochlorite (5.25%). Samples were cleansed with distilled water and the adhesive bonding of the dentine surface was performed and restored with light cure nanohybrid resin composite. Samples were longitudinally sectioned perpendicular to the adhesive interfaces and prepared according to test before and after thermocycling. Results: For microtensile bond test, control group and minocycline showed highest significant microtensile bond strength in comparison with chlorohexidine and sodium hypochlorite immediately and after thermocycling. While no significant difference was found between different groups for failure mode analysis. For nanoleakage, control group and minocycline showed the least nanoleakage. For hybrid layer resin tag length evaluation control group, minocycline and chlorohexidine groups showed almost similar resin tag penetration while sodium hypochlorite showed the highest penetration for resin tags. Conclusions: Usage of minocycline matrix metalloproteinase inhibitor showed promising results concerning bond strength and nanoleakage on contrary to chlorohexidine. Sodium hypochlorite results showed decreased bond strength, increased nanoleakage and resin tag length.