To evaluate the effect of two different deproteinizing agents (5.25% sodium hypochlorite and Papacarie®) prior to acid etching on the shear bond strength and microleakage of a fissure sealant material. A total of 123 extracted noncarious human third molar teeth were randomly divided into three groups for each test: acid etching alone (control) (C), sodium hypochlorite (NaOCl), and Papacarie Duo® (PC). The shear bond strength tests were performed using a universal testing machine, and microleakage was evaluated using a dye penetration method. The mean shear bond strength values obtained in Group C were significantly lower than those of Group NaOCl and Group PC (p=0.0001). There were no significant differences between Group NaOCl and Group PC (p>0.05). No statistically significant difference was observed among the groups in terms of microleakage (p>0.05). Papacarie Duo® and 5.25% sodium hypochlorite treatments before etching increased the shear bond strength of the fissure sealant. However, pre-treatment with these agents did not decrease the microleakage between teeth and sealant.