A series of novel imidazole-blocked diisocyanate bioadhesives (IBAs) were synthesized from reaction of toluene 2, 4-diisocyanate (TDI), isophorone diisocyanate (IPDI), hydroxyl-terminated polylactide (HO-PLA-OH), 1,1,1-trimethylolpropane (TMP), and imidazole. Synthesis of IBAs was confirmed by Fourier transform infrared spectroscopy (FTIR) and gel permeation chromatography (GPC). Differential scanning calorimetry (DSC) and thermal gravimetric analysis (TGA) revealed that the TDI-based IBA had lower thermal dissociation temperature and a faster deblocking rate than IBA based on IPDI. Hydroxyl-terminated polyurethane (HPU) was introduced to study the adhesive effect of the synthesized IBAs. Improvement on elastic modulus, tensile strength and water resistance of IBA-modified HPU in comparison with neat HPU suggested the good adhesive effect of IBA due to the strong chemical reaction between released NCO groups from IBA and hydroxyl groups from HPU.