This work aimed at developing a natural compound-based hydrogel adsorbent to remove diclofenac as a model pharmaceutical from water. First, graphene oxide–chitosan (GO–CTS) and amine graphene oxide–chitosan (AGO–CTS) hydrogel adsorbents were synthesized via a facile mechanical mixing method. The synthesized materials were characterized through Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), Brunauer–Emmett–Teller (BET), scanning and transmission electron microscopy (SEM and TEM), Raman spectroscopy, and thermogravimetric analysis (TGA) techniques. In the second stage, adsorption experiments were conducted to determine the best GO to CTS ratio and find the optimized adsorption parameters, including the initial drug concentration, adsorbent dosage, pH, and temperature. The results showed that the optimal GO to CTS mass ratio is 2 : 5 and thus the same ratio was selected as the AGO to CTS mass ratio to understand the effect of amine-functionalization on removal efficiency. The optimal adsorption parameters were determined to be pH of 5, C_i of 100 ppm and dosage of 1.5 g L⁻¹, where 90.42% and 97.06% removal was achieved for optimal GO–CTS and AGO–CTS hydrogel adsorbents, respectively. Langmuir and Freundlich isotherms models were employed to investigate the adsorption behavior of diclofenac onto the synthesized hydrogels. The results revealed that the adsorption tends to be of the monolayer type and homogeneous, as the results were in better accordance with the Langmuir model than the Freundlich model. The thermodynamics of adsorption demonstrated that the adsorption is exothermic, exhibiting higher removal efficiency at lower temperatures. Furthermore, Gibb's free energy change of adsorption (ΔG) suggested that the adsorption is spontaneous, being more spontaneous for AGO–CTS than GO–CTS hydrogels. Finally, the regeneration ability of the hydrogel adsorbents was studied in five consecutive cycles. The adsorbent maintained its efficiency at a relatively high level for three cycles but a considerable decrease was observed between the third and the fourth cycle, indicating that the hydrogels were recoverable for three cycles.