Biological sterilization represents one of the most exciting applications of atmospheric pressure glow discharges (APGD). Despite the fact that surgical instruments are contaminated by both microorganisms and proteinaceous matters, sterilization effects of APGD have so far been studied almost exclusively for microbial inactivation. This work presents the results of a detailed investigation of the capability of a helium-oxygen APGD to inactivate proteins deposited on stainless-steel surfaces. Using a laser-induced fluorescence technique for surface protein measurement, a maximum protein reduction of 4.5 logs is achieved by varying the amount of the oxygen admixture into the background helium gas. This corresponds to a minimum surface protein of 0.36 femtomole/mm2. It is found that plasma reduction of surface-borne protein is through protein destruction and degradation, and that its typically biphasic reduction kinetics is influenced largely by the thickness profile of the surface protein. Also presented is a complementary study of possible APGD protein inactivation mechanisms. By interplaying the protein inactivation kinetics with optical emission spectroscopy, it is shown that the main protein-destructing agents are excited atomic oxygen (via the 777 and 844 nm emission channels) and excited nitride oxide (via the 226, 236, and 246 nm emission channels). It is also demonstrated that the most effective protein reduction is achieved possibly through a synergistic effect between atomic oxygen and nitride oxide. This study is a useful step toward a full confirmation of the efficacy of APGD as a sterilization technology for surgical instruments contaminated by prion proteins.