Perfluorooctanoic acid (PFOA), a widely used perfluorinated alkyl substance (PFAS), poses significant environmental and health risks. This study investigates PFOA adsorption in the existence of natural organic matter (NOM) using granular activated carbon (GAC) modified with dielectric barrier discharge (DBD) plasma. PFOA’s amphiphilic structure, characterized by a hydrophilic carboxyl group head and a hydrophobic perfluorinated tail, contributes to its versatility and persistence. The selection of the Chao Phraya River (CPR) water as the NOM source, captures the complexity of a major water body subjected to diverse pollution sources. The results were analyzed through the Toth and Temkin isotherm models. Application of the Toth isotherm model reveals enhanced PFOA adsorption capacity in CPR water compared to DI water, emphasizing the influence of NOM. The Temkin isotherm analysis further characterizes the strength and efficiency of the adsorption process, highlighting a stronger interaction between PFOA and plasma-modified GAC in CPR water. The study indicates that the adsorption process in CPR water may be more influenced by PFOA surface coverage on the GAC surface in the presence of NOM. Overall, this research contributes valuable insights into pollutant removal strategies, highlighting the potential of DBD plasma-modified GAC in addressing PFOA contamination challenges in water systems.