To assess the remineralizing potential of dentin matrix proteins and enamel matrix derivatives (DMPs and EMDs) after application on artificially induced dentin lesions, given the hypothesis that these materials increase the mineral uptake, binding, and mineralization. Forty-eight caries-free human premolars were used. Teeth were cut, polished, and embedded, leaving an open window on the root surface, of which one-third was covered with a flowable composite to preserve the healthy untreated dentin. Then, samples were demineralized in Buskes solution for 33 days. A micro-CT scan prior to treatment was performed. Next, the samples were randomly allocated into four groups: (A) An untreated negative control (CON), (B) application of porcine dentin matrix proteins (DMP), (C) treatment with enamel matrix derivatives (EMD, Emdogain, Straumann), and (D) amine fluoride application (AMF, Elmex fluid, GABA). All samples were placed in artificial saliva for 21 days. A second micro-CT scan was performed, after which the change in gray scaling within a defined region of interest (0.25 mm3) was analyzed. ANCOVA was applied to discover statistical differences between the different treatments. Both, treatment with AMF; (P = 0.011 versus CON) as well as with DMP (P = 0.043 versus CON) yielded a statistically significant difference compared to the control treatment. EMD treatment was not found to differ (P > 0.05). Mainly the top layer of the defects showed clear signs of remineralization, which was also evident in CON. This study was able to visually confirm the remineralization potential of demineralized dentin especially after DMP application, which, however, did not outperform AMF. Based on this, additional studies combining proteins and fluorides are now warranted and ongoing.