The inappropriate release of pharmaceutical residues into different environmental matrices has become a major concern around the world, since drugs and their metabolites can cause adverse effects on ecosystems and human health. Because of this, several studies have been carried out with the aim of removing these emerging contaminants from the aquatic environment through remediation methods. Thus, this research aims to understand the thermodynamic aspects involved in the removal of the drugs sodium cromoglycate (CG) and diclofenac sodium (DF) in aqueous solution through the adsorption process using cross-linked chitosan. The cross-linked chitosan (QR) samples and the others that were subjected to the adsorption process were characterized by infrared absorption spectroscopy, X-ray diffraction, zeta potential, scanning electron microscopy and thermogravimetry techniques. Regarding the adsorption equilibrium analyzes in a binary system, they were carried out using four different temperatures (15, 25, 35 and 45°C) and in the ternary at 25°C. To estimate the parameters of the adsorption isotherms, the experimental data were fitted with the following adsorption isotherms: Langmuir, Freundlich, Sips, Redlich-Peterson and Frumkin. To this end, the drugs, separated or mixed in aqueous solution, were quantified through the development of calibration curves obtained from experimental data measured by the UV-Vis spectrophotometry method. The results revealed that in binary systems the thermodynamic parameters of adsorption at low concentrations of adsorbate indicated an exothermic nature for CG, while for DF it was endothermic. Furthermore, entropic factors played a very important role, especially for DF, with adsorption being more favorable for CG. At high concentrations, the situation is reversed, that is, DF adsorption becomes more favorable, being endothermic for both drugs. In relation to adsorption in ternary systems, at lower concentrations, CG adsorption is favored, mainly because it has a lower Gibbs adsorption free energy. At a certain critical concentration, the adsorption changes drastically, in the form of a clear discontinuity in the adsorption isotherm, after this discontinuity, at higher concentrations, the adsorption is favored for the DF, due to the attractive interaction of the lateral parameters. Finally, it was shown that drugs adsorb spontaneously on the QR surface, being another alternative particle that can be applied in the treatment of effluents that contain pharmacological residues.