Worldwide studies on contamination levels of anti-inflammatory drugs such as ibuprofen (IBF) show that their concentration in water bodies is increasing. Graphene oxide/palladium nanoparticle (Pd NPs-GO) was synthesized via a simple solvothermal method. The characteristics of the as-prepared samples were examined using X-ray fluorescence, scanning electron microscopy, and Fourier transforms infrared spectroscopy. The performance of Pd NPs-GO nanocomposite as a sonocatalyst was evaluated for the degradation of IBF under ultrasonic irradiation (35 kHz), and compared with graphene (GO) and palladium nanoparticle (Pd NPs). Some influencing parameters such as IBF initial concentration, pH, catalyst dosage, and irradiation time were investigated. The findings showed that Pd NPs-GO nanocomposite exhibited higher sonocatalyst activity for IBF than other catalysts. A higher ibuprofen degradation efficiency was observed in lower pH (3), lower initial concentration (30 mg/L), higher catalyst dosage (2 g/L), and higher ultrasonic irradiation time (50 min). The kinetics of the degradation of IBF followed pseudo-first-order reaction kinetics.