Chronic inflammation is a typical feature and a major impediment in refractory diabetic foot ulcer (DFU). High levels of extracellular cell-free nucleic acid (cfDNA) have recently been known to play a critical role in the cause of inflammation. Herein, we fabricated polyacrylamide-based cationic hydrogels and topically applied them to the ulcer of a diabetic rat model. The cfDNA level in the wound area was significantly reduced after hydrogel adsorption, and the level of inflammation was eliminated. In turn, the wound closure was significantly promoted without introducing systemic toxicity. Cationic hydrogels represent an effective material to combat uncontrolled inflammation in DFU.