Organobentonites have been applied for the removal of two common non-steroidal anti-inflammatory drugs, ibuprofen (IBU) and diclofenac sodium (DS), from aqueous solutions. Two surfactants, one with and the other without benzyl group (octadecyldimethylbenzylammonium chloride, ODMBA, and hexadecyltrimethylammonium bromide, HDTMA), in amounts equivalent to 50, 75, and 100% of the cation exchange capacity of bentonite were used for the preparation of organobentonites. Successful modification of bentonite was confirmed by several methods: X-ray powder diffraction (XRPD), point of the zero charge (pHPZC), determination of exchanged inorganic cations in bentonite, determination of textural properties, and scanning electron microscopy (SEM). Kinetic and thermodynamic data on the adsorption of IBU and DS showed that drug adsorption was controlled by the type and the amount of surfactant incorporated into the bentonite and by their arrangement in the interlayer space and at the surface of organobentonites. The adsorption of both drugs increased with an increase in the amount of both surfactants in organobentonites. The presence of the benzyl group in organobentonites enhanced the adsorption of IBU and DS and was more pronounced for IBU. Drug adsorption fits the pseudo-second-order kinetic model the best. The thermodynamic data revealed that the adsorption process was endothermic in nature and with increase of the amount of both surfactants drug adsorption processes were more spontaneous. The results obtained from this study revealed that adsorbents based on surfactants modified bentonite are promising candidates for IBU and DS removal from contaminated water.