Sol-gel coating technology was applied to modify the bonding surface of self-glazed zirconia (SZ). Its effect on the bond strength of SZ to enamel was evaluated in vitro in comparison with the conventional milled zirconia treated by airborne-particle abrasion (CZa) and the heatpressed lithium disilicate glass-ceramics treated by etching and silanization (LDe). All ceramic specimens were bonded to the etched bovine enamel with adhesive resin cement. Shear bond strength of both sol-gel coated SZ groups with different strategies (SZc1 and SZc2) was 20.00 ± 7.07 MPa and 18.32 ± 3.63 MPa, respectively, which was comparable to that of LDe, 18.44 ± 2.27 MPa (p > 0.05) and significantly higher than that of CZa, 11.72 ± 1.48 MPa, and SZ, 3.06 ± 1.66 MPa (p < 0.05). Lots of voids between zirconia clusters were observed on the bonding surface of SZc1, yet that of SZc2 showed homogeneous honeycomb nanoporous structure. All groups exhibited mixed failure except SZ, and the fracture surfaces of SZc1, SZc2, and LDe showed better wettability than CZa. Sol-gel coating could improve the bond strength of SZ to enamel, and the sol-gel coated SZ might have the potential to make minimally invasive restorations.