Hybrid nanocomposites (NCs) produced by the dispersion of zinc oxide (ZnO) nanoparticles (NPs) in thermoplastic poly(amide-imide)s (PAIs) are designed and synthesized using ultrasonic-assisted technology. ZnO NPs were functionalized with 3-aminopropyltriethoxysilane (KH550) coupling agent to increase the hydrophobic nature of NPs. Reaction of diamine containing N-(4-hydroxyphenyl) benzamide and a diacid chloride comprising pyromellitoyl-bis-L-isoleucine segments at low temperature provided the polymeric matrix with well-designed groups. Surface treatments of ZnO NPs gave a better dispersion and enhancing possible interactions of NPs with functional units of polymer matrix. The surfacemodified ZnO NPs were dispersed uniformly in the PAIs matrix using ultrasonic irradiation. The obtained NCs were characterized by Fourier-transform infrared spectroscopy, x-ray powder diffraction, atomic force microscopy, fieldemission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM) and thermogravimetry analysis. The FE-SEM and TEM pictures confirmed the globular-like structures for NCs.