To evaluate the potential of an additional application of two novel hydrophobic experimental adhesive resins with or without bioactive zinc fluoride glass to promote the bond strength of a one-step self-etch universal adhesive. Three self-etch universal adhesives, G-Premio Bond (GPB), Scotchbond Universal (SBU) and Clearfil SE Bond 2 (SE2), and two experimental adhesive resins, BZF210 and BZF21, were used in this study; thus, five groups were formed: GPB, GPB+BZF210, GPB+BZF21, SBU, and SE2. The adhesives were applied to flat dentin surfaces according to each manufacturer's instructions. The microtensile bond strengths (μTBS) were evaluated after 24-h water storage. The fracture modes and interfacial structures were analyzed using SEM, while elemental analysis was performed using SEM-EDS. The data were analyzed using one-way ANOVA and the Games-Howell test (p < 0.05). Significantly higher μTBS was achieved by additional application of BZF210 (48.68 ± 6.59 MPa) and BZF21 (58.58 ± 2.84 MPa) compared with GPB (33.57 ± 4.22 MPa) alone. Most failures occurred above the smear layer in GBP, while more cohesive and mixed failures were observed in GBP+BZF210, GPB+BZF21, SBU, and SE2. The interfacial structures revealed that GBP+BZF210 and GPB+BZF21 had more and longer resin tags than did GPB. SEM-EDS showed a particularly high peak of zinc in GPB+BZF21. The bond strength of GPB was significantly improved by the additional application of BZF210 and BZF21. Using an additional bioactive hydrophobic layer on a one-step, self-etch universal adhesive can significantly improve its bonding efficacy and extend its clinical options.