This study reports the analysis of diclofenac removal from aqueous solution using a novel adsorbent coating with amphoteric surface. This adsorbent coating was improved using a new amphoteric ratio to increase its performance for the removal of pharmaceuticals such as diclofenac. The adsorbent coating was formulated using acrylic polymer emulsion, smectite-based clay powder and epichlorohydrin-dimethylamine to obtain a layer form via the implementation of a facile synthesis method. In a previous study, this adsorbent coating was successful to remove cationic and anionic dyes. Therefore, this research aimed to further investigate and test its application in the removal of other emerging water pollutants like pharmaceuticals. SEM, EDX, and FTIR analyses were carried out for the characterization of this novel adsorbent. The effects of adsorbent composition, diclofenac concentration, temperature, and solution pH were studied and modeled. The best conditions to improve the diclofenac adsorption was 303 K and pH 3 where the adsorption capacity was 25.59 mg/g. Adsorption isotherms and kinetics were quantified and modeled, and the corresponding adsorption mechanism was also analyzed. Diclofenac adsorption with this novel material was exothermic and spontaneous. This alternative adsorbent is promising for diclofenac removal from industrial wastewater systems.