A strong graphene oxide (GO)-based artificial nacre is developed by using a simple and efficient interfacial chemistry. GO is simultaneously reduced and functionalized with tannic acid (TA) and the resulting TA-reduced GO (TA-RGO) exhibits a high aqueous dispersibility owing to abundant phenol groups. TA-RGO sheets are incorporated with poly(vinyl alcohol) (PVA) and then assembled into an artificial nacre-like structure by vacuum-assisted filtration to induce the formation of multidentate interfacial hydrogen bonding between TA-RGO and PVA. Based on the multidentate hydrogen bonding, the resulting TA-RGO/ PVA (1 wt%) composite film presented an overall and efficient reinforcement of tensile strength (186.1 ± 12.8 MPa), modulus (15.2 ± 1.2 GPa) and toughness (1546 ± 248 kJ/m3) compared to those of GO (83.3 ± 5.4 MPa, 8.9 ± 0.4 GPa and 1434 ± 152 kJ/m3) and TA-RGO (87.6 ± 10.6 MPa, 13.8 ± 1.4 GPa and 306 ± 51 kJ/m3), respectively. The present study demonstrates the rational design of interfacial interaction can greatly improve the performance of a structural composite material.