Inflammatory bowel disease (IBD), a chronic inflammatory gastrointestinal disease, is closely related to diverse inflammatory factors like reactive oxygen and nitrogen species (RONS) and cell-free DNA (cfDNA). Herein, tannic acid (TA) modified hafnium hydride nanosheets (HfH(1.983)@TA NSs) with a thickness of 1-4 nm, prepared by liquid-phase exfoliation, were explored as a high-performance anti-inflammatory agent for IBD treatment. By virtue of the high specific surface area of two-dimensional structure, HfH(1.983)@TA NSs can effectively not only scavenge RONS, but also eliminate cfDNA, thus inhibiting the pro-inflammatory responses. In a dextran sodium sulfate (DSS)-induced IBD mouse model, HfH(1.983)@TA NSs by oral administration rapidly alleviated various IBD symptoms, including disease activity index (DAI), colon length, and the level of pro-inflammatory cytokines in 5 days, superior to the clinical drug 5-aminosalicylic acid (5-ASA). This work introduces ultrathin hafnium hydride nanosheets with RONS and cfDNA-dual scavenging capabilities as efficient two-dimensional anti-inflammatory agents for IBD treatment.