This study was set to assess the possible benefits of novel cavity disinfectants with 5% dimethylaminododecyl methacrylate (DMADDM); and compare the effectiveness of saliva microbial-aging method with water-aging in measuring the changing of resin-dentin bond strength. Three cavity disinfectants were tested: 0.2% Chlorhexidine (CHX); 5% DMADDM; and 5% DMADDM + 0.2% CHX. Microtensile bond strength (μTBS) test was performed after microbial-aging with saliva microbial or water aging for one month. Hydroxyproline (HYP), the production of collagen degradation, was measured spectrophotometrically. Additionally, the antibacterial effects of each reagent were evaluated. The 5% DMADDM exerted the least percentage of resin-dentin bond strength loss after one month microbial-aging ( < 0.05). There were no statistically significant differences of bond strength decrease after one month water aging among the tested groups ( > 0.05). Microbial-aging method yield more drop of bond strength than water aging in all groups except 5% DMADDM ( < 0.05). Meanwhile, 5% DMADDM had the same matrix metalloproteinases (MMPs) inhibitory effects as the other two agents ( > 0.05), but much stronger antibacterial capability than 0.2% CHX ( < 0.05). This indicated that a cavity disinfectant with 5% DMADDM is promising for improving the stability of resin-dentin bonds in appearance of saliva biofilm; and the saliva microbial-aging method is more promising for studying the durability of resin-dentin bonds than water aging.