The aim of this study was to understand the effect of Zn-doping of adhesives and mechanical load cycling on the micromorphology of the resin-dentin interdiffusion zone (of sound and caries affected dentin). The investigation considered two different Zndoped adhesive approaches and evaluated the interface using confocal laser scanning microscopy. Sound and carious dentin-resin interfaces of unloaded specimens were deficiently resin-hybridized, in general. These samples showed a rhodamine B-labeled hybrid layer and adhesive layer completely affected by fluorescein penetration (nanoleakage) through the porous resin-dentin interface, but thicker after phosphoric acid-etching and more extended in carious dentin. Zn-doping promoted an improved sealing of the resin-dentin interface at dentin, a decrease of the hybrid layer porosity, and an increment of dentin mineralization. Load cycled augmented the sealing of the Zn-doped resin-dentin interfaces, as porosity and nanoleakage diminished, and even disappeared in caries-affected dentin substrata conditioned with EDTA. Sound and carious dentin specimens treated with the xylenol orange technique produced a clearly outlined fluorescence when resins were Zn-doped, due to a consistent Ca-mineral deposits within the bonding interface and inside the dentinal tubules, especially when load cycling was applied on specimens treated with Zn-doped bonding components of self-etching adhesives. Micropermeability at the resin-dentin interface diminished after combining EDTA pretreatment, ZnCl2-doping and mechanical loading stimuli on restorations. It is clearly preferable to include the zinc compounds into the bonding constituents of the self-etching adhesives, instead of into the primer ingredients. The promoted new mineral segments contributed to reduce or avoid both porosity and nanoleakage from the load cycled Zn-doped resin dentin interface.