Currently, no dressings are utilized after removal of polyps during a colonoscopy rendering these tissue sites susceptible to bleeding, sepsis, and perfusion. We report the design specifications, synthesis, and ex vivo evaluation of in situ polymerized hydrogels as colon wound dressings post polypectomy. The hydrogels exhibited varied properties to include moduli between 100 and 16 000 Pa, dissolution times between 4 h to 7 days or longer, swelling up to 200%, and adhesion to colon tissue from 0.1 to 0.4 N/cm². The hydrogels displayed minimal cytotoxicity, prevented the migration/spread of bacteria, and exhibited rapid gelation, a requirement for application to the lumen of the colon via an endoscope. This work highlights the structure–property relationship of hydrogels prepared from N-hydroxysuccinimide functionalized PEG cross-linkers and hyperbranched polyethylenimines or 4-arm PEG-NH₂ star polymers, and their potential as colon wound dressings.