Considering the probability of chemical and enzymatic reactions between matrix metalloproteinases (MMPs) in the dentin structure and their specific inhibitors, the aim of the present study was to evaluate the effect of different concentrations of specific inhibitor of MMPs (galardin) on the shear bond strength of self-adhesive resin cements to dentin. Forty-eight sound human premolars were mounted in self-cured acrylic resin after removal of the enamel on the buccal and lingual surfaces. The dentin surfaces achieved were polished and prepared with 600-grit silicon carbide paper. The samples were divided into 3 groups (n=16) based on the concentration of galardin used (with no galardin, galardin at a high concentration and galardin at a low concentration). In addition, 96 composite resin blocks, measuring 3 mm in height and diameter, were prepared. The composite resin blocks were bonded to the buccal and lingual surface dentin with Rely-X Unicem (RXC) and Speed CEM (SPC) self-adhesive resin cements, respectively, according to manufacturers? instructions. After 24 hours of storage in distilled water at 37°C, the shear bond strength values were determined in MPa and fracture modes were evaluated under a stereomicroscope. Data were analyzed with two-way ANOVA and post-hoc Bonferroni test (?=0.05). The shear bond strength of galardin at high concentration was significantly higher than that in the control group and galardin at a low concentrations (P<0.001). In addition, galardin at a low concentration exhibited higher shear bond strength compared to the control group (P=0.005). Furthermore, higher shear bond strength values were reported with the use of RXC compared to SPC (P<0.001). Irrigation with galardin increased the shear bond strength of self-adhesive resin cements to dentin and this increase had a direct relationship with the concentration of galardin in the solution.