Crohn’s disease (CD) and ulcerative colitis are chronic inflammatory bowel diseases (IBD) of which the etiology and pathogenesis are not completely understood. In paediatric patients, the disease tends to be more severe and aggressive then in adults. Here, we perform a proteomic approach on ascending colon biopsies from 119 pediatric patients to characterize disease pathogenesis and the impacts of treatment. Consistent with previous findings, we report an altered proteome in IBD patients that indicates impaired mitochondrial function. Gene ontology revealed that proteins downregulated in inflammation are associated with metabolism, whereas upregulated proteins contribute to protein processing. A comparison of proteomes from CD patients before and after therapeutic intervention identified over 100 proteins that are significantly different between patients that responded and those that did not respond to therapy; creatine kinase B was elevated before treatment in patients with mucosal healing after treatment, whereas basigin increased after treatment in responsive patients.