The ideal treatment option for immature necrotic permanent teeth is regeneration of the pulp–dentin complex. Mineral trioxide aggregate (MTA), the conventional cement used for regenerative endodontic procedures, induces hard tissue repair. Various hydraulic calcium silicate cements (HCSCs) and enamel matrix derivative (EMD) also promote osteoblast proliferation. The purpose of the present study was to determine the osteogenic and dentinogenic potential of commercially distributed MTA and HCSCs when applied in combination with Emdogain gel on human dental pulp stem cells (hDPSCs). The presence of Emdogain resulted in greater cell viability, and higher alkaline phosphatase activity was detected in the Emdogain-supplemented groups in the early days of cell culture. On qRT–PCR, the groups treated, respectively, with Biodentine and Endocem MTA Premixed in the presence of Emdogain showed an increased expression of the dentin formation markerDSPP, and the group treated with Endocem MTA Premixed in the presence of Emdogain showed an upregulated expression of the bone formation markersOSXandRUNX2. In an Alizarin Red-S staining assay, all of the experimental groups exhibited a greater formation of calcium nodules when treated in combination with Emdogain. Overall, the cytotoxicity and osteogenic/odontogenic potential of HCSCs were similar to that of ProRoot MTA. The addition of the EMD increased the osteogenic and dentinogenic differentiation markers.