Background: Acute intestinal infections in children are a considerable medical and social problem worldwide. Immune therapy could help to reduce the frequency of post-infectious functional intestinal dysfunction in patients with comorbidities. Aim: To evaluate the efficacy of human recombinant interferon alpha-2b, administered at acute phase of an acute invasive intestinal infection to infants in the first months of age, suffering from functional bowel disorders. Materials and methods: This was an open-label, randomized (envelope method), prospective study in two parallel groups. The study included 59 infants of the first months of life, who were breastfed, had a history of intestinal dysfunction and were hospitalized to an infectious department. We studied efficacy of recombinant interferon alpha-2b administered in rectal suppositories at a dose of chromatography with measurement of short-chain fatty acids. Results: Standard treatment was ineffective in 63.3% (95% CI 43.9–80.0%) of patients. Administration of interferon alpha-2b reduced the rate of treatment failure by day 14 to 32% (95% CI 9–56%) and the risk of persistent diarrhea for more than one month to 29% (95% CI 5–53%). In those patients who were administered interferon, inflammation at days 25 to 55 was less severe and the levels of i-forms of short-chain fatty acids were lower. Conclusion: Immunotherapy with recombinant interferon alpha-2b seems to be a promising way to improve combination treatment of acute invasive intestinal infections in infants with a history of intestinal dysfunction, as it reduces the risk of post-infectious intestinal disorders.