This work describes the surface modification of 300PEO-PEOT/PBT 55/45 thin films using a medium pressure dielectric barrier discharge system operated in argon, helium, nitrogen or dry air to improve cell-surface interactions of this established biomaterial. The first part of the paper describes the optimization of the plasma processing parameters using water contact angle goniometry. The optimized samples are then characterized for changes in surface topography and surface chemical composition using atomic force microscopy (AFM) and X-ray fluorescence spectroscopy (XPS) respectively. For all plasma treatments, a pronounced increase in surface wettability was observed, of which the extent is dependent on the used plasma discharge gas. Except for dry air, only minor changes in surface topography were noted, while XPS confirmed that the changes in wettability were mainly chemical in nature with the incorporation of 5–10% of extra oxygen as a variety of polar groups. Similarly, for the nitrogen plasma, 3.8% of nitrogen polar groups were additionally incorporated. Human foreskin fibroblast (HFF) in vitro analysis showed that within the first 24 h after cell seeding, the effects on cell-surface interactivity were highly dependent on the used discharge gas, nitrogen plasma treatment being the most efficient. Differences between untreated and plasma-treated samples were less pronounced compared to other biodegradable materials, but a positive influence on cell adhesion and proliferation was still observed.