Antibiotic contaminants in water and wastewater can cause serious damage to the environment and human health. Hence, their effective removal from water matrices is crucial. Effective removal of antibiotics using the adsorption process is a promising technique thanks to its easy regeneration, low cost, and high efficiency. In this work, the adsorption of amoxicillin (AMX) was investigated on a synthesized flexible metal−organic framework MIL-53(Al). The MIL-53(Al) adsorbent with a high surface area was synthesized using the hydrothermal method. It was then characterized by N 2 adsorption− desorption, FE-SEM, TEM, XRD, FT-IR, EDS, and TG analyses. The batch adsorption experiments were performed to examine the effects of solution pH, ionic strength, contact time, adsorbent dosage, and initial AMX concentration. Furthermore, the adsorption mechanism and adsorption kinetics as well as isotherms were studied experimentally. The adsorption kinetics indicated that the adsorption process was more compatible with the pseudo-secondorder kinetic model. The equilibrium adsorption data were well fitted using the Langmuir model. The MIL-53(Al) exhibited an excellent saturated adsorption capacity of 758.5 mg g −1 at 303 K and pH = 7.5 ± 0.1, surpassing all previous reported MOF-based adsorbents. The adsorption process was spontaneous and exothermic, although the entropy value decreased during the adsorption process. Furthermore, the MIL-53(Al) adsorbent had a good regeneration and reusability such that the adsorption capacity diminished slightly after reuse for four cycles. These results revealed that MIL-53(Al) would be a promising adsorbent for the adsorption of AMX from water matrices for environmental protection.