Nano-sized activated carbon was prepared from pomegranate peel (PG-AC) via NaOH chemical activation and was fully characterized using BET, FT-IR, FE-SEM, EDX, and XRD. The newly synthesized PG-AC was used for cefixime removal from the aqueous phase. The effective parameters on the adsorption process, including solution pH (2–11), salt effect (0–10%), adsorbent dosage (5–50 mg), contact time (5–300 min), and temperature (25–55 °C) were examined. The experimental adsorption equilibrium was in close agreement with the type IV isotherm model set by the International Union of Pure and Applied Chemistry (IUPAC). The adsorption process was evaluated with isotherm, kinetic, and thermodynamic models and it is were well fitted to the Freundlich isotherm (R2 = 0.992) and pseudo-second-order model (R2 = 0.999). The Langmuir isotherm provided a maximum adsorption capacity of 181.81 mg g−1 for cefixime uptake onto PG-AC after 60 min at pH 4. Hence, the isotherm, kinetic and thermodynamic models were indicated for the multilayer sorption followed by the exothermic physical adsorption mechanism.