Polyamide-12/Portland cement nanocomposite was prepared by using the exfoliated adsorption method. The fabricated nanocomposite was applied first time to remove Congo red (CR), brilliant green (BG), methylene blue (MB), and methyl red (MR) from the synthetic wastewater. The polymer nanocomposite was characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, energy-dispersive X-ray spectroscopy, elemental mapping, Brunauer–Emmett–Teller surface area analysis, and X-ray diffraction. The adsorption was rapid and all the studied dyes were absorbed on the surface of the polymer nanocomposite in 90 min. The point of zero charge was found at pH 5 and the factors such as pH, time, and temperature were found to affect the adsorption efficiency. Freundlich isotherm and pseudo-second-order models well-fitted the adsorption isotherm and kinetics data, respectively. The calculated maximum adsorption capacity was 161.63, 148.54, 200.40, and 146.41 mg/g for CR, BG, MB, and MR, respectively. The mode of the adsorption process was endothermic, spontaneous, and physical involving electrostatic attraction. On an industrial scale, the high percentage of desorption and slow decrease in the percentage of adsorption after every five regeneration cycles confirm the potential, practicality, and durability of the nanocomposite as a promising and advanced adsorbent for decolorization of colored wastewater.