Purpose: To investigate the effect of the dimethyl-sulfoxide wet-bonding technique on composite-dentin bonds and to explore its potential mechanism. Materials and Methods: Thirty human third molars were segmented, ground, etched, and randomly divided into three groups according to the following pretreatments: 1. water; 2. ethanol; 3. 50% (v/v) dimethyl sulfoxide (DMSO). Then, Single Bond 2 was applied and composite buildups were constructed. After 24 h of water storage or 10,000 cycles of thermocycling, the microtensile bond strength (MTBS) and nanoleakage were measured. Contact angle measurement, Masson's trichrome staining, and in situ zymography were used to explore the possible action mechanism of DMSO on adhesive-dentin interfaces. Results: DMSO pretreatment prevented the decline of thermocycled MTBS (p 0.05) without affecting the immediate MTBS (p > 0.05) compared to the water wet-bonded group. Nanoleakage expression in the thermocycled DMSO wet-bonded group was also less than that in the thermocycled water-wet group (p 0.05). Moreover, DMSO decreased the contact angle of the dentin surfaces (p 0.05), reduced the amount of collagen exposure (p 0.05), and decreased the collagenolytic activity in the hybrid layer (p 0.05). Conclusion: The 50% DMSO pretreatment was effective in increasing the wettability of the etched dentin surface, promoting the penetration of the adhesive monomer, and enhancing the stability of the dentin collagen at the adhesive-dentin interface. All these changes may lead to higher quality dentin bonds, suggesting that DMSO wet bonding is a viable alternative to improve the durability of dentin bonding. Keywords: DMSO wet, ethanol wet bond, dentin bonding, collagen exposure, durability