Red mud (RM) is the industrial waste of alumina production and causes serious environmental risks. In this paper, a novel activation procedure for RM (mechano-chemical processing) is proposed in order to improve the nitrate adsorption from water. High-energy milling and acidification were selected as mechanical and chemical activation methods, respectively. Synthesized samples of adsorbent were produced considering two parameters of activation: acid concentrations and acidification time in two selected milling times. Optimization of the activation process was based on nitrate removal from a stock solution. Experimental data were analyzed with two-way analysis of variance and Kruskal–Wallis methods to verify and discover the accuracy and probable errors. Best conditions (acceptable removal percentage > 75) were 17.6% w/w for acid concentrate and 19.9 minutes for acidification time in 8 hours for milling time. A direct relationship between increase in nitrate removal and increasing the acid concentration and acidification time was observed. The adsorption isotherms were studied and compared with other nitrate adsorbents. Characterization tests (X-ray fluorescence, X-ray diffraction, Fourier transform infrared spectrophotometry, dynamic light scattering, surface area analysis and scanning electron microscopy) were conducted for both raw and activated adsorbents. Results showed noticeable superiority in characteristics after activation: higher specific area and porosity, lower particle size and lower agglomeration in structure.