This study aims to contribute to understanding the removal processes of diclofenac potassium (DP) medicine in wastewater treatment systems, employing activated carbon (AC) as an adsorbent. To achieve this goal, a multidisciplinary approach was adopted, integrating experimental and theoretical analyses of equilibrium data regarding the adsorption of DP on AC. Five statistical physics models were applied to determine the model best for the adsorption process. The selection of the most appropriate model considered both the performance of the models and the analysis of the estimated parameters. Statistically, all models exhibited satisfactory results. However, when analyzing the estimated parameters, the double-layer model with single adsorption energy emerged as the most suitable model to describe the analyzed process. Based on the chosen model’s parameters, we observed that as the temperature increases, the number of active sites occupied during adsorption and their availability on the adsorbent also increases. However, the number of available adsorption sites decreases as the temperature rises. The half-saturation concentration, in turn, increases with increasing temperature, suggesting that the process is favored when temperatures above room temperature are used. Additionally, higher temperatures provide better removal results, indicating that DP molecules’ non-parallel and parallel orientations on the AC surface favor the adsorption process. Finally, our combined results led to the proposal of a mechanism for DP adsorption on AC, which is based on physical adsorption interactions between adsorbate-adsorbent and adsorbate–adsorbate.