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Nowadays, water pollution represents a serious problem both for agriculture and human health. Find innovative strategy for a large-scale removal of pollutants from wastewaters is thus a challenge. In this context, both cyclodextrin derivatives and clay minerals have been used as low-cost nanomaterials for the sorption of pollutants because of their features. Cyclodextrin derivatives are particularly recognized for the removal of organic chemicals, drugs, and pesticides from wastewater. Hectorite (Ht), a clay mineral of smectite group, shows high cation exchange capacity and negatively charged basal surfaces that could allow the removal both of heavy metal ions and organic pollutants. Herein, the synthesis of a hybrid organic/inorganic nanomaterial based on the chemical modification of Ht by grafting modified β-cyclodextrin units is reported. In this way systems with complementary and synergistic adsorption ability for removal of both organic pollutants and heavy metal ions were developed. Two different synthetic approaches were investigated, and the obtained nanomaterials were subjected to thorough structural characterization by FT-IR and 13C solid state NMR spectroscopies, dynamic light scattering, and ζ-potential measurements and the loading of organic moieties was verified by thermogravimetric analysis. In addition, the morphology was investigated by high angle annular dark field transmission electron microscopy (HAADF/STEM) coupled with energy dispersive X-ray spectroscopy (EDX). The synthetized nanomaterial was tested as a sorbent for the removal of antibiotics, organic dyes and heavy metal ions. Finally, the simultaneous filtration of ciprofloxacin and Pb(II) ions, chosen as models, from simulated wastewater by a column filtration laboratory prototype was investigated, too. [Display omitted] • The synthesis of organic/inorganic nanomaterial based on hectorite and β-cyclodextrin is reported. • The nanomaterial was tested as a sorbent for the removal of different pollutant • Thanks to cyclodextrins the nanomaterial showed better adsorption performance than hectorite • Recycling tests showed that the nanomaterial can be reused for at least 4 cycles. • A laboratory column filtration system was set up to simultaneously remove different pollutants [ABSTRACT FROM AUTHOR]