To investigate the clinical efficacy and side effects of gamma globulin combined with methylprednisolone pulse therapy in the treatment of acute disseminated encephalomyelitis in children. Methods: Fifty-six children with acute disseminated encephalomyelitis were selected and randomly divided into the simple group and combined group with 28 cases in each group. The 2 groups were both treated with methylprednisolone pulse therapy while the combined group was additionally given gamma globulin. The recovery time of symptoms were compared between the 2 groups. The expanded disability status scale (EDSS) score before treatment, after 1 week of treatment, and after 1 month of treatment and clinical efficacy were compared, and drug side effects and sequelae were also monitored. Results: The recovery time of symptoms of the combined group were shorter than those of the simple group (P<0.05). The EDSS scores at 1 week and 1 month of treatment of both groups were lower than those before treatment, and the EDSS scores at 1 month of treatment of both groups were lower than those at 1 week of treatment; moreover, scores of the combined group at 1 week and 1 month of treatment were lower than those of the simple group (P<0.05). There was a significant difference in the clinical efficacy grade distribution between the 2 groups (P<0.05), and the total effective rate of the combined group was higher than that of the simple group (P<0.05). There was no significant difference in the incidence rates of total adverse reactions and the occurrence rates of sequelae between the 2 groups (P>0.05). Conclusion: Gamma globulin combined with methylprednisolone pulse therapy in the treatment of children with acute disseminated encephalomyelitis can significantly accelerate the relief of clinical symptoms, promote the recovery of nerve function, and improve therapeutic effect. Furthermore, it is relatively safe and can reduce sequelae to a certain extent.