This study reports the tailoring of surface chemistry of palm fibers via plasma for the adsorption of sodium diclofenac from aqueous solution. Surface functionalization of palm fibers was carried out with three feeding gases: humid air, air saturated with hydrogen peroxide and air saturated with sodium hydroxide. Functionalized palm fibers were physicochemical characterized and their diclofenac adsorption properties were compared. Diclofenac adsorption tests were performed at different operating conditions (initial concentration, particle size, pH and temperature). Kinetics and isotherms of the diclofenac adsorption on raw and plasma-based functionalized fibers were quantified and modeled with different equations. Thermodynamic parameters of diclofenac adsorption were estimated and statistical physics calculations were carried out to characterize the adsorption orientation of diclofenac molecules on biomass surface. Overall, the palm fibers functionalized with plasma and hydrogen peroxide showed the best adsorption properties for the removal of this pharmaceutical. Results showed that diclofenac adsorption was a multi-molecular exothermic process with an inclined adsorption orientation on the fiber surface. The experimental maximum adsorption capacities decreased from 33.12 to 24.71 mg/g at 25–50 °C. Liu model provided the best correlation of experimental data for all adsorption temperatures. Solution pH played a relevant role in the diclofenac adsorption mechanism where hydrogen bonding, van der Waals forces and electrostatic interactions were involved. This paper contributes to the valorization of biomasses for implementing low-cost and effective adsorption processes to face the water pollution caused by pharmaceuticals.