Cellulose is a versatile biopolymer increasingly applied in medicine and industry due to its biodegradability and biocompatibility, along with the renewability and large availability of source materials. However, finding simple, eco-friendly, and effective methods to modify cellulose to provide it with new functionalities remains a challenge. This work presents a new, inexpensive, and eco-friendly method to chemically modify microcrystalline cellulose (MCC) by the submerged cold plasma treatment of an aqueous suspension of MCC containing different oxidizing agents, such as hydrogen peroxide (H