The prevalence of autoimmune hepatitis (AIH) is increasing, yet specific pharmacotherapies remain to be explored. The present study aimed to investigate the effects of sophoricoside (SOP), a bioactive component of medical herbs, on AIH and to elucidate the underlying mechanisms. Bioinformatic approaches were used to predict the potential targets and underlying regulatory mechanisms of SOP on AIH. The effects of SOP on AIH were evaluated by determining the expression levels of inflammatory cytokines, histological liver injury and hepatic fibrosis in an improved chronic cytochrome P450 2D6 (CYP2D6)‑AIH mouse model and in a model of concanavalin‑A (ConA)‑induced acute immune‑mediated liver injury. The antioxidant activity of SOP was detected in in vivo and in vitro experiments. The selected signal targeted by SOP in AIH was further confirmed using western blot analysis and immunofluorescence staining. The results of bioinformatic analysis revealed that the targets of SOP in AIH were related to oxidative stress and the NF‑κB gene set. The NF‑κB transcription factor family is a key player that controls both innate and adaptive immunity. The activation of the NF‑κB signaling pathway is often associated with autoimmune disorders. In the animal experiments, SOP attenuated CYP2D6/ConA‑induced AIH, as evidenced by a significant reduction in the levels of hepatic enzymes in serum, inflammatory cytokine expression and histological lesions in the liver. The oxidative response in AIH was also significantly inhibited by SOP, as evidenced by a decrease in the levels of hepatic malondialdehyde, and elevations in the total antioxidant capacity and glutathione peroxidase levels. The results of the in vivo and in vitro experiments revealed that SOP significantly reduced the enhanced expression and nuclear translocation of phosphorylated p65 NF‑κB in the livers of mice with AIH and in lipopolysaccharide‑stimulated AML12 cells. On the whole, the present study demonstrates the protective role of SOP in AIH, which may be mediated by limiting the oxidative response and the activation of the NF‑κB signaling pathway in hepatocytes.