Gastrointestinal disorders, such as irritable bowel syndrome (IBS) and inflammatory bowel diseases (IBD, including Crohn’s disease and ulcerative colitis), affect 10–15% of the global population resulting in a substantial socioeconomic burden on our society.^[1] Mucosal biofilms are mucus-adherent prokaryotic communities embedded in a protective layer of extracellular substances displaying high antibiotic resistance^[2] and occur in 57% of IBS patients and 34% of ulcerative colitis patients.^[3] Animal venom is a rich source of bioactive peptides that have been fine-tuned throughout evolution for diverse physiological activities. Numerous venom-derived peptides display potent antimicrobial activity, representing valuable therapeutic opportunities for treating infectious diseases.^[4] However, the full potential of such peptides against gut mucosal biofilms has not been revealed yet. Our approach focuses on developing gut biofilm-targeting peptides, including (i) synthesis of venom-derived peptides from diverse animal species, (ii) screening for biofilm-specific activity against bacterial isolates from biofilm-positive patients, and (iii) chemical strategies to improve our leads’ gut stability and therapeutic window. Here, we report our latest results in developing venom-derived antibiofilm peptide therapeutics for treating mucosal biofilms in patients with gastrointestinal disorders.