The aim of this research was to assess the influence of mechanical loading on the ability of Zn-free versus Zn-containing amalgams to promote remineralization at the dentin interface. Sound and caries-affected dentin surfaces (CAD) were restored using Zn-free or Zn-containing dental amalgams. Midcoronal dentin surfaces were studied by (1) atomic force microscopy analysis (including plot and phase imaging, nanoindentation test [modulus of Young (Ei), nanoroughness measurements, and fibril diameter assessment], (2) Raman spectroscopy/cluster analysis, (3) x-ray diffraction, (4) field emission electron microscope and energy-dispersive analysis, for morphological, mechanical, and physicochemical characterization. Analyses were performed before amalgam placement and after amalgam removal, at 24 h and 3 weeks of load cycling. Zn-free and Zn-containing amalgams restorations promoted an increase in the modulus of Young of CAD surfaces, after 3 weeks of load cycling; at this time, Zn-containing amalgams attained higher Ei than Zn-free restorations. Zn-containing amalgams induced tubular occlusion after load cycling, in both sound and CAD. Zn free-amalgams promoted remineralization of both intertubular and peritubular dentin in CAD substrata. These minerals were identified as calcium-phosphate deposits and crystals as hydroxyl-apatite with augmented crystallographic maturity but with some components of lattice distortion. Crosslinking of collagen diminished and secondary structure of collagen increased in CAD substrate restored with Zn-containing amalgam after 3 weeks of load cycling, indicating an advanced preservation, molecular organization, and orientation of collagen fibrils after load cycling. Plot and phase images permitted to observe the topographical changes which were promoted by the mineral deposits; in general, the indexes related to higher remineralization gave rise to a decrease of nanoroughness and an augmentation of the bandwidth of the collagen fibrils. Zn-containing amalgam restorations submitted to mechanical stimuli promote remineralization of the partially mineral-depleted subjacent substrate at the caries-affected dentin.