• This study introduces a simple method for non-harmful natural adsorbent preparation and modification using different acids and bases with convenient and accessible desorption. • The characterization results indicated that clinoptilolite nanoparticles were well prepared and preparation method was effective. • The achieved results from Design Expert showed that at D/C and pH equal to 81.53 and 6.5, respectively the optimal percentage of the iron removal is obtained with value equal to 97.97%. • Freundlich isothermal model best described the total iron adsorption process, and it has been observed that maximum adsorption capacity is 50 mg/g for the total iron removal. Nanotechnologies present a promising application in the production of water to obtain potable water from natural sources by treatment. Clinoptilolite is an abundant and low-cost natural zeolite, which has adsorbent properties. Moreover, this study introduces a simple method for non-harmful natural adsorbent preparation and modification using different acids and bases with convenient and accessible desorption. The characterization methods used in this study are X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Response Surface Method (RSM) has been utilized to reflect the influence of operations variables in Design Expert 7.0. Other Variables, including the Effect of Modifications, contact time, the percentage of the dosage of adsorbent to the beginning (initial) pollutants concentration (D/C), and pH on total iron, were researched during the research procedure. The characterization results indicated that clinoptilolite nanoparticles were well prepared, and the preparation method was effective. Best modification Performance was shown in Z10(0.1 M Hydrochloric Acid dried by Air) at 24 h Setting time. The achieved results from Design Expert showed that at D/C and pH equal to 81.53 and 6.5, respectively, the optimal percentage of the iron removal is obtained with a value equal to 97.97%. In addition, Freundlich isothermal model best described the total iron adsorption process, and it has been observed that the maximum adsorption capacity is 50 mg/g for the total iron removal.