Emulsion polymer isocyanate (EPI) adhesive is one of the most widely used structural adhesives in the woodworking industry. However, there has been a lack of knowledge on how the EPI-adhesive interacts with the chemical constituents of wood, in particular, with the wood extractives that are known to influence the bonding quality. In this study, the interactions of the EPI-adhesive with the water extracts and selected extractives from European wood species were systematically investigated using different analytical techniques. While the alterations in the curing properties of the pure EPI-adhesive and EPI-adhesive-extract mixtures were revealed by in situ rheology and Fourier-transform infrared spectroscopy, evolved gas analysis, and pyrolysis-gas chromatography/mass spectrometry, the solid-state 13C nuclear magnetic resonance were performed for analyzing the final chemical composition of the cured adhesive. Moreover, the influence of the extraction on the mechanical bonding performance was tested by tensile-shear tests. The study revealed significant interactions between the EPI-adhesive and tannin-rich, acidic wood extracts. The acidic chestnut and oak extracts catalyzed the curing reactions and led to a huge increase in the adhesive viscosity. These interactions might affect the bonding quality, for example, adhesive penetration depth and formation of bonding strength, therefore, careful attention is required when bonding acidic wood surfaces.