Background: Children with short bowel syndrome (SBS) have abnormal intestinal anatomy, secretion, or motility, which can lead to small intestinal bacterial overgrowth (SIBO). In this paper, we describe our experience with SIBO in children with SBS, focusing on potential risk factors, clinical presentation, and antibiotic treatment. Methods: A single-center retrospective descriptive cohort study of all episodes of clinically suspected SIBO in 16 children with SBS on home parenteral nutrition (HPN) between January 2018 and December 2022 was performed. Results: The mean small bowel remnant was 47 cm (SD = 31.5), with an absent ileocecal valve in 61.5% (8/13). Five children (31.2%) had at least 1 episode of clinically suspected SIBO, with a total of 25 episodes. The most common clinical presentation was diarrhea (76%), followed by meteorism (56%), loss of appetite (48%), flatulence (48%), weight loss (36%), abdominal pain (25%), and vomiting (12%). Fifty-six percent (16/25) of SIBO episodes were treated with one type of antibiotic, 36% (9/25) with two types, and 8% (2/25) with three types. Symptom resolution was achieved in 56% (14/25) of SIBO episodes after one course of antibiotic therapy. Two children (12.5%) had refractory and recurrent SIBO episodes treated with cyclic antibiotic regimens. Conclusions: SIBO can affect the ability of children with SBS to successfully wean off HPN. Diagnostic tests have innate challenges, and early clinical suspicion is paramount. Antibiotic therapy should be individualized considering the child's age, gastrointestinal anatomy, and the risk of SIBO recurrence.