Plasma medicine is an attractive new research area, but fundamental information related to plasma modification of biomacromolecules in aqueous solution remains elusive. As described herein, we investigated the chemical effects of low‐temperature atmospheric pressure plasma on protein in aqueous solution using lysozyme as a model. Plasma treatment decreased enzymatic activity and changed the secondary structure that results from the increased molecular weight of lysozyme with chemical modification. These effects arise neither from UV light nor from plasma heat, suggesting that the reactive species generated by the plasma affect lysozyme. The information presented in this paper represents a crucial first step for elucidating chemical reactions induced by plasma on proteins for biomedical applications.