Adequate functioning of the intestinal barrier is required in order to repel invading pathogens while tolerating commensal microbiota and self-antigens. Inflammatory bowel diseases (IBDs), encompassing Crohn's disease (CD) and ulcerative colitis (UC), are characterized by disrupted intestinal barrier integrity, resulting in excessive passage of luminal antigens and the activation of aberrant immune responses against otherwise unexposed antigens. A comprehensive overview of the exact antigens associated with IBD is still lacking, but recent innovative antibody profiling technologies have enabled systematic characterization of humoral immunity in health and disease. Here, we review established serological antibodies and novel high-throughput methods, such as protein arrays, phage-display immunoprecipitation sequencing (PhIP-Seq), and B cell receptor sequencing (BCRseq), and provide an outlook on their applications in disease diagnostics, therapeutic interventions, and opportunities for prevention in IBD.