Adsorption separation technology is a widely used technology for the separation and the purification of gases and liquids in a wide range of fields. Processes such as pressure swing adsorption (PSA) present an interesting tool for biogas upgrading. The performance of PSA process is controlled by many parameters such as number of beds, cycle step durations, pressure ratio, recycle rate and most importantly the nature and the characteristics of the adsorbent. The selection of an appropriate adsorbent for bio-methane production from biogas by pressure swing adsorption remains a key element for enhancing the performance of PSA technology. Reported experimental results on bio-methane, upgrade from biogas using PSA, show that the performance is highly dependent on the different used adsorbents. In order to rationalize the process of adsorbent selection for a given biogas feed composition, we have developed an approach based on numerical simulations, at the reactor level, of a PSA process used to upgrade the biogas in bio-methane with CH4 purity higher than 98%. These simulations were coupled to molecular-based simulation for optimizing the adsorbent that gives the best performance for a given feed composition. We use the optimal adsorbent characteristics for selecting available adsorbents having similar characteristics. In order to validate the selection of the adsorbents, a series of experimental tests ranging from pure component adsorption isotherms to breakthrough adsorption experiments are carried out together with dynamic flow conditions where the selected adsorbents are characterized using CO2/CH4 gas mixtures. The effects of feed flow rate, number of beds, cycle step durations and purge-to-feed ratio are studied. The optimal operating parameters of the process are obtained from simulations. This cycle will be then tested in PSA pilot plants for biogas upgrading purposes.