Hybrid-layer degradation occurs because of acidic properties of currently used adhesive systems. Titanium tetrafluoride couples with tooth surface, and titanium compounds are not substituted. Caffeic acid phenethyl esther inhibits endogenous matrix metalloproteinases that cause hybrid-layer degradation. It was hypothesized that titanium tetrafluoride and caffeic acid phenethyl esther application on exposed dentine surfaces before adhesive applications would inhibit nanoleakage and hybrid-layer degradation without compromising the bond strength of the adhesives. In ultracut thin sections, human dentine-chemical agent-adhesive composite interfaces were observed under transmission electron microscope with complementary scanning electron microscopy. Microtensile bond strength tests were also accomplished. Titanium tetrafluoride and titanium tetrafluoride + caffeic acid phenethyl esther applications decreased bond strength values. Caffeic acid phenethyl esther showed decreased silver nitrate penetration for cements based on Bisphenol glycydilmethacrylate and methyl methacrylate, whereas cement based on 4-methacryloyloxyethyl trimellitate anhydride methyl methacrylate showed almost no infiltration. Caffeic acid phenethyl esther application before cementation could inhibit nanoleakage and biodegradation of the hybrid layer.