BackgroundClostridioides difficile(C. difficile) is the major pathogen causing antibiotic-associated diarrhea. There are a variety of symptoms associated withC. difficileinfection (CDI) in adults, including self-limiting diarrhea, pseudomembranous colitis, toxic megacolon, septic shock, and even death from the infection. However, the infant’s intestine appears to be completely resistant to the effects ofC. difficiletoxins A and B with rare development of clinical symptoms.Case presentationIn this study, we reported a 1-month-old girl with CDI who was born with neonatal hypoglycemia and necrotizing enterocolitis. Her symptom of diarrhea occurred after extensive use of broad-spectrum antibiotics during hospitalization and was accompanied by elevated white blood cell, platelet, and C-reactive protein levels, and repeated routine stool examinations were abnormal. She was recovered by norvancomycin (an analogue of vancomycin) and probiotic treatment. The results of 16 S rRNA gene sequencing also demonstrated the recovery of intestinal microbiota with the enrichment ofFirmicutesandLactobacillus.ConclusionsBased on the literature review and this case report, clinicians should also pay attention to diarrhea caused byC. difficilein infants and young children. More strong evidence is needed to explain the true prevalence of CDI in this population and to better understand theC. difficile-associated diarrhea in infants.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13099-023-00552-1.