Bacterial infection and excessive inflammation following abdominal injury can cause life-threatening complications that lead to multiple organ failure and death. Removing bacteria and proinflammatory factors-which are predominantly negatively charged-from the wound site with a cationic, antibiotic-containing hydrogel wound dressing is therefore a promising treatment approach for severe abdominal trauma. Here an injectable, self-healing hydrogel composed of the gel-forming glycosaminoglycan oxidized chondroitin sulfate (OCS), cationic polyethylenimine (PEI), and the antibiotic tobramycin (Tob) via a Schiff's base reaction is developed. Compared with hydrogels lacking either PEI or Tob, only the Tob/PEI/OCS hydrogels exhibit a large binding capacity for negatively-charged proinflammatory factors including cell-free DNA, lipopolysaccharides, TNF-α, and high mobility group box 1 protein, and a large reduction in bacterial populations in vitro. In a murine model of severe abdominal trauma, the Tob/PEI/OCS hydrogel exhibits good biodegradability and biosafety, reduced local and systemic inflammation and infection, and prevents multiple organ failure, resulting in 100% survival. This hydrogel dressing is thus a promising biomaterial for preventing complications and improving outcomes following severe abdominal trauma.