In this article, an atmospheric dielectric barrier discharge (DBD) plasma reactor was used as a novel tool for the upgrading of bio-oil using anisole as a model compound. The influences of different carrier gases (Ar, H-2, and He) on the performance of the reactor were carefully studied. The results revealed that the conversion of anisole in He plasma is higher than that in Ar or H-2 plasma. This may be attributed to the more stable and homogeneous discharge of He plasma. It is believed that in all of the experiments phenoxy radical was formed as the primary product of anisole dissociation via electron-attack reactions. Moreover, the most abundant product was phenol, which was formed by the free-radical reaction between phenoxy and H radicals. It was found that the upgrading of anisole involved demethylation, transalkylation, and hydrogenolysis reactions. In addition to phenol, 4-methylanisole, 2-methylphenol, benzene, 4-methylphenol, 2,6-dimethylanisole, and cyclohexane were also formed in the reactor. Furthermore, the effect of applied voltage and pulse frequency on the performance of He plasma were carefully investigated. As the voltage and frequency were increased, the quantity and quality of efficient collisions between active species and anisole molecules increased, resulting in an increase in anisole conversion and specific input energy of the discharge. The highest conversion of anisole was 72.7%, which was obtained in a He plasma at an applied energy of 9 kV and a pulse frequency of 20 kHz. Under these conditions, the average input power and specific input energy of the discharge were 71.2 W and 42.7 kJ/mL. The results imply that the DBD plasma reactor is a promising tool for the upgrading of anisole.