Developing a low‐cost depyrogenation process is vital in extending the medical applicability of polymers that can be used in medicine. We present an overview of the plasma‐based depyrogenation literature and address the need to develop a nonthermal plasma‐based depyrogenation process for delicate materials such as chitosan. We present a low‐cost plasma apparatus to treat chitosan powder in hermetically sealed bags. We decouple the experiments into two parts: depyrogenation experiments for dried standard endotoxin on glass slides and analysis of chitosan modifications through Fourier‐transform infrared spectroscopy. We demonstrate depyrogenation efficacy with up to a 4‐log reduction in endotoxin levels and discuss minor changes observed in plasma‐treated chitosan.