Cellulose recalcitrance is one of the major barriers in converting renewable biomass to biofuels or useful chemicals. A pretreatment reactor that forms a dielectric barrier discharge plasma at the gas-liquid interface of the microbubbles has been developed and tested to pretreat alpha-cellulose. Modulation of the plasma discharge provided control over the mixture of species generated, and the reactive oxygen species (mainly ozone) were found to be more effective in breaking-up the cellulose structure compared to that of the reactive nitrogen species. The effectiveness of pretreatment under different conditions was determined by measuring both the solubility of treated samples in sodium hydroxide and conversion of cellulose to glucose via enzymatic hydrolysis. Solutions pretreated under pH 3 buffer solutions achieved the best result raising the solubility from 17% to 70% and improving the glucose conversion from 24% to 51%. Under the best conditions, plasma-microbubble treatment caused pronounced crevices on the cellulose surface enhancing access to the reactive species for further breakdown of the structure and to enzymes for saccharification.