A natural clinoptilolite nanostructure (CNS) along with ultrasonic irradiation was used to remove Cu2+ ions from polluted water. In the first part of this work, natural clinoptilolite was converted to CNS by ball milling. The natural clinoptilolite and prepared CNS samples were characterized by scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy, Fourier-transform infrared (FTIR) spectroscopy, X-ray diffraction, N2 adsorption/desorption and pH at the point of zero charge analyses. The SEM images showed the development of CNS from natural clinoptilolite by ball milling. The N2 adsorption/desorption and FTIR spectroscopy confirmed the greater specific surface area, pore volume and number of surface groups of the CNS compared to the natural clinoptilolite. In addition, the crystalline phase of the CNS was the same as the natural clinoptilolite. In the second part of this work, the ultrasonic-assisted sorption of Cu2+ ions from polluted water by CNS was investigated. These experiments were optimized with response surface methodology based on central composite designs. The effects of initial pH of solution, CNS dosage, sonication time and temperature on Cu2+ ion-removal efficiency were investigated. By using a CNS dosage of 500 mg L−1, an initial pH of 6, a sonication time of 12 min and a sonication temperature of 45°C as optimal conditions, 97% of Cu2+ ions were removed from contaminated water. The initial pH was the most effective variable. Ultrasonic-assisted sorption of Cu2+ was more effective than sorption alone, onto the CNS.