This research aimed to study the effect of desensitizing toothpaste containing strontium acetate and toothpaste containing arginine on the effectiveness of two bonding agents in class V cavities restored with resin composite. Cavity preparations were performed on buccal root surface of 65 permanent premolar teeth. The teeth were divided into 6 groups consisting of the use Scotchbond™ Universal Adhesive after brushing with Sensodyne® Rapid Relief, Colgate® Sensitive Pro-Relief™ and no brushing, compared to teeth bonded with Scotchbond™ Multi-Purpose Adhesive after brushing with the same toothpastes and no brushing. All teeth were restored with resin composite. After thermocycling and immersion in silver nitrate solution, the teeth were sectioned and evaluated using 4-interval scores under a stereomicroscope. The results showed that leakage score of Scotchbond™ Multi-Purpose Adhesive groups were statistically significantly higher than that of Scotchbond™ Universal Adhesive groups. However, Scotchbond™ Universal Adhesive groups demonstrated significantly difference between each group. Meanwhile, for Scotchbond™ Multi-Purpose Adhesive groups, there was no statistical difference among toothpastes and no brushing. In this study, it was concluded that both toothpastes did not have any effect on microleakage of Scotchbond™ Multi-Purpose Adhesive, whereas Colgate® Sensitive Pro-Relief™ showed more microleakage than Sensodyne® Rapid Relief when using with Scotchbond™ Universal Adhesive.