Treatment the deeper and remineralizable carious zone (DRCZ) in dentin with various remineralizing methods, either with classic top-down or biomimetic bottom-up remineralization approaches, has remained a constant main issue to enhance dentin substrate bonding quality. The concern of remineralizing the remaining, partially demineralized and physiologically re-mineralizable collagen fibrils was the optimum target. However, applying already mineralized type I collage fibrils which have the ability to chemically cross-link with remaining collagen and minerals did not gain much interest. Synthesis of collagen/hydroxyapatite (Col/Hap) nanocomposite was done with self-assembling Hap in situ onto Col fibrils with different % (70/30, 50/50, 30/70% of Col/Hap, respectively). Micro-tensile bond strength (μTBS) was evaluated after pre-treatment of artificially demineralized dentin with these suggested protocols [nanocomposite together with grape seed extract (GSE; 6.5%) cross-linker for two periods, 10min and 1 h] then applying self-adhesive bonding system. Applied Col/Hap (30/70%) together with GSE (6.5%) gave the significantly highest μTBS (25.04 ± 5.47 and 25.53 ± 7.64 MPa, for 10min and 1 h application times, respectively). After thermocycling for 10,000 cycles at 5 and 55 ◦C, μTBS for all protocols and both application times substantially decreased especially for the two control groups. Using the suggested dentin pre-treatment protocols, in chair-side, may possibly enhance the bond strength to DRCZ and its durability.