Wood adhesives can serve as one of the key components to manufacture wood composites. Their selection has a profound impact on the resulting wood products. Wood composites are also required for the fundamental yield, high value-added, and cost-effective production. At the same time, some issues are increasingly concerned on the formaldehyde emissions from wood composites, since formaldehyde was already recognized as a cancerogen to human beings back in 2004. As a result, the wood composites processing has been shifted to formaldehyde-free adhesives in recent years. Polymeric diphenylmethane diisocyanate (pMDI) can serve as the isocyanate wood adhesive in the wood industry, due to its exceptional water and solvent resistance, formaldehyde-free nature, and high strength. World demand for isocyanates is expected to increase significantly to 15.74 billion U.S. dollars by the next decade, indicating the large market potential of isocyanates and their wide application prospects. Despite the advancements in isocyanate adhesive technologies, the inherent low viscosity of pMDI and the "over-penetration" during hot-pressing have posed great challenges to the widespread applications. Alternatively, wheat straw is normally perceived as low-value agricultural waste, due to its chemical composition of cellulose, hemicellulose, and lignin, all of which contain hydroxyl groups. These hydroxyl-rich components can react with isocyanate groups to form strong carbamate bonds, thus resulting in a complex three-dimensional cross-linked network that is reinforced by hydrogen bonding. In this study, wheat straw microparticles were introduced to incorporate as a functional filler in the isocyanate wood adhesives, in order to strengthen the adhesion performance of the products. The results showed that the dry/wet bonding properties of straw-modified isocyanate adhesive were improved under conventional hot-pressing pressures (0.8-1.2 MPa) at weak pressure conditions (0.1 MPa). Moreover, the reactivity of the modified adhesive remained after adding straw with 9% moisture content; On the contrary, the dry strength, 24 h cold water soaking strength, and “boiling-drying-boiling” strength reached 4.07, 3.41 and 3.23 MPa, respectively, under weak pressing condition of 0.1 MPa. The strengths increased by 145%, 142%, and 197% after straw particles, respectively, compared with the control group without straw. Further characterizations indicated that the straw particles formed a stable crosslinked structure with isocyanate in the curing process, which significantly promoted the consistency of bonding interfaces; Therefore, the weak hot-pressing pressure was achieved in the high adhesive strength of wood adhesives.