Purpose: This study was conducted to evaluate the biological pulp response to Pulpine and Polyamidoamine Dendrimer and their combination in dogs and comparing their remineralizing potentials on human caries affected dentin. Materials and Methods: Forty-five teeth in 3 mongrel dogs were randomly divided into 3 groups according to the applied pulp capping material; group A1: Pulpine NE, group A2: PAMAM G3 and group A3: Pulpine and PAMAM. Class V cavities were prepared; the pulps were mechanically exposed and finally restored with resin modified glass ionomer. Histological evaluation was performed after 2 weeks, 1 and 2 months. The in vivo study was designed as a randomized, unicenter, parallel, two arms, double–blind split mouth clinical trial with 1:1 allocation ratio. The subjects who fulfilled the eligibility criteria were asked to participate and signed informed consent. Twenty-eight adhesive occlusal cavities were prepared; infected dentin was removed leaving carious affected dentin at the pulpal floor and divided into 2 groups; P1 (Pulpine) and P2 (Pulpine and PAMAM). Remineralization was assessed radiographically at base line, 1, 3 and 6 months. Results: In the animal study, there was no statistically significant difference among the tested direct pulp capping materials regarding the inflammation intensity, dentin bridge continuity or morphology. For the clinical trial, P2 group showed statistically significant higher dentin density at all study intervals. Conclusion: Pulpine and PAMAM enhanced pulp tissue repair. PAMAM could induce biomimetic remineralization of caries affected dentin.