The purpose of this study was to evaluate if mechanical loading influences bioactivity and bond strength at the resin–dentin interface after bonding with Zn-doped etch-and-rinse adhesives. Dentin surfaces were subjected to demineralization by 37% phosphoric acid (PA) or 0.5 M ethylenediaminetetraacetic acid (EDTA). Single bond (SB) adhesive—3M ESPE—SB+ZnO particles 20 wt% and SB+ZnCl2 2 wt% were applied on treated dentin to create the groups PA+SB, SB+ZnO, SB+ZnCl2, EDTA+SB, EDTA+ZnO, and EDTA+ZnCl2. Bonded interfaces were stored in simulated body fluid for 24 h and tested or submitted to mechanical loading. Microtensile bond strength (MTBS) was assessed. Debonded dentin surfaces were studied by high-resolution scanning electron microscopy. Remineralization of the bonded interfaces was assessed by atomic force microscope imaging/nanoindentation, Raman spectroscopy/cluster analysis, and Masson’s trichrome staining. Load cycling (LC) produced reduction in MTBS in all PA+SB, and no change was encountered in EDTA+SB specimens, regardless of zinc doping. LC increased the mineralization and crystallographic maturity at the interface; a higher effect was noticed when using ZnO. Trichrome staining reflected a narrow demineralized dentin matrix after loading of dentin surfaces that were treated with SB-doped adhesives. This correlates with an increase in mineral platforms or plate-like multilayered crystals in PA or EDTA-treated dentin surfaces, respectively.