This study presents an analysis of the structure and properties of different types of lignocellulosic fillers modified by isophorone diisocyanate (IPDI) to provide insights into the possibility of their application to the manufacturing of wood polymer composites (WPCs). Moreover, it deals with the environmental aspects of modified fillers, by assessment of volatile organic compounds (VOCs) emitted during modification, as well as from final products. Three types of commercially available lignocellulosic fillers were modified with different content of IPDI (from 1 to 15 wt%) using the internal mixer. The main compounds detected in the air during modifications were terpenes and terpenoids. No IPDI was detected, which is very beneficial considering its toxicity. On the other hand, IPDI was emitted from modified fillers at a slightly elevated temperature of 40 °C, which was associated with a significant rise in its vapor pressure. Successful modification of fillers was confirmed by FTIR spectroscopy and thermogravimetric analysis. Performed modifications of lignocellulosic fillers with IPDI had a relatively small impact on their particle size and color properties. Such an effect can be considered beneficial for the mechanical performance and appearance of WPCs, which could be potentially manufactured using IPDI-modified lignocellulosic fillers.