This study was carried out to investigate the remineralizing effect of amorphous calcium phosphate (ACP) and calcium fluoride (CaF2) nanoparticles incorporated in two-step self etch- adhesives (in vivo). Materials and Methods: The nanoparticles were incorporated into the bond of ClearfilTM SE Bond at a mass fraction of 10%. A total of ten patients in the age range of 17-30 years old, having at least 3 carious lower molars, were enrolled in this study (split mouth design). Class I cavity preparation was performed, leaving the caries affected dentine at the pulpal floor. The 30 molars were divided into 3 groups (n=10) according to the type of adhesive used (A); namely: self-etch adhesive, Clearfil SE Bond (Control)(A1), Clear Fill SE Bond incorporated with ACP NPs (A2) and Clearfil SE Bond incorporated with CaF2 NPs (A3). After restoration placement, each tooth was radiographically evaluated at baseline (I0), after 1 month (I1) and after 3 months (I2) to assess the remineralizing effect of the adhesive systems used. Results: The adhesive containing ACP nanoparticles induced the highest remineralization potential during all the study intervals, followed by the adhesive containing (CaF2) nanoparticles. Conclusion: nanoparticles are capable of remineralizing the caries affected dentin when incorporated into two-step self etch adhesive