This study aimed at investigating the effect of a methacrylate-modified chitosan on the durability of adhesive interfaces to improve the clinical performance of dental restorations. Chitosan was modified with methacrylic acid (Chit-MA70) on 16% of the amino groups. Viscosity, rheology, and H-1 NMR spectroscopy were performed to characterize the modified polysaccharide. Chit-MA70 was blended into a primer of an etch-and-rinse experimental adhesive system and tested on human teeth. The presence of methacrylate moieties and of residual positive charges on the polysaccharide chain allowed Chit-MA70 to covalently bind to the restorative material and electrostatically interact with demineralized dentin. The Chit-MA70 containing an adhesive system showed values of the immediate bond strength (26.0 +/- 8.7 MPa) comparable to the control adhesive system (25.5 +/- 8.7 MPa). However, it was shown that upon performing thermo-mechanical cycling treatment of the dental restoration on human teeth, the adhesive with the methacrylate-modified chitosan, in variance with the control adhesive, did not show any decrease in the bond strength (28.4 +/- 8.8 MPa). The modified chitosan is proposed as a component of the etch-and-rinse adhesive system to efficiently improve the durability of dental restorations.