Purpose: In order to provide an experimental basis for the use of baicalein (BAI) as an enzyme inhibitor to improve resin-dentin bonding durability, this study explored the effect of BAI on the expression of matrix metalloproteinases (MMPs) and cathepsins in human dental pulp cells (HDPCs). Materials and Methods: The effects of various concentrations of BAI on the viability and cell cycle arrest of HDPCs were investigated in vitro. qPCR and Western blot analysis were performed to determine the effects of BAI on the expression of MMP-2, MMP-9, cathepsin-B, and cathepsin-K in HDPCs. Thermocycling (aging) was performed to determine the effect of BAI on the microtensile bond strength of aged resin-dentin bonding. Results: Our results showed that BAI at concentrations below 25 μmol/l did not affect cell viability in HDPCs. Moreover, low concentrations of BAI effectively inhibited the expression of MMP-2, MMP-9, cathepsin-B, and cathepsin-K in HDPCs and improved the strength of aged resin-dentin bonding. Conclusion: BAI is a promising preconditioner for improving the durability of resin-dentin bonding by protecting against collagen degradation via the inhibition of MMPs and cathepsins. Keywords: baicalein, matrix metalloproteinases, cathepsins, human dental pulp cells, resin-dentin bonding