Boron nitride nanotubes (BNNTs) are inappropriate for further chemical derivatization because of their chemical inertness. We demonstrate covalent activation of chemically inert BNNTs by isophorone diisocyanate (IPDI) to form isocyanate group (NCO)-terminated BNNT precursors with an 'NCO anchor' ready for further functionalization. As identified by Fourier transform infrared spectroscopy, a number of molecules or polymers with -COOH, -OH or -NH₂ groups are readily attached to the activated IPDI-BNNTs. The IPDI-BNNT-involving polymer composites have shown mechanical properties are considerably improved due to the good dispersibility of IPDI-BNNTs in the polymer matrix and the strong interfacial interactions between BNNTs and polymers. The methodology reported here provides a promising method to promote the chemical reactivity of BNNTs and covalently modify polymer nanocomposites with improved mechanical performance.