Adsorption of diclofenac sodium (DCF) from aqueous solutions using surface-modified/oxidized activated carbons (OACs) was investigated and compared with that over virgin activated carbon (AC). The obtained results showed a remarkable increase (∼6 times) in DCF removal over oxidized AC compared to that over a commercial, unmodified AC, despite the decreased surface area in the OAC. The large increase in DCF removal may be due to the presence of acidic surface functional groups, which are created on the AC surface upon oxidation. To understand the role of these acidic functional groups on the increased adsorption capacity (qt), the concentration of acidic groups was determined using Boehm titration after oxidation with different quantities of oxidizing agent. The adsorption capacity of the OAC prepared by treatment with 2.0 M ammonium persulfate solution (OAC (2.0)) was the highest of the prepared adsorbents. Therefore, OAC (2.0) was studied in detail by characterizing the material and investigating the adsorption performances. The effect of pH on the surface charge (zeta potential) and DCF adsorption capacity of OAC (2.0) was investigated to lead to the mechanism of DCF adsorption such as hydrogen bonding and electrostatic interactions. Additionally, the OAC can be recycled for adsorptive removal of DCF by simple solvent washing. Therefore, the OAC was found to be a promising adsorbent for the removal of DCF from contaminated water.