This research endeavors to investigate the potential preventive and protective effects of chlorogenic acid (CGA), a bioactive component found in various foods, in the context of dextran sodium sulfate (DSS)-induced colitis in mice. The study reveals that CGA administration, at dosages of 150 and 300 mg/kg, significantly retards the progression of colitis. This is substantiated by observable enhancements in colon length, reduction in the disease activity index, and mitigation of colon tissue damage. Meanwhile, CGA acts as an antioxidant by reducing the oxidative stress associated with colitis inflammation and increasing the activity of antioxidant enzymes. Furthermore, CGA demonstrates anti-inflammatory properties by inhibiting the inflammatory response associated with colitis and regulating the excessive expression of cytokines. Notably, CGA contributes to the restoration of intestinal barrier function by augmenting the levels of claudin-1 and ZO-1. Moreover, the investigation uncovers CGA's capacity to modulate the gut microbiota composition in colitic mice, fostering the proliferation of beneficial bacteria, notably Lactobacillus, while concurrently impeding the growth of detrimental bacteria like Bacteroides, Enterobacteriaceae, and Escherichia_Shigella. To conclude, these findings substantiate the viability of CGA for diverse applications in the realms of food and medicine, thereby bolstering its potential as a therapeutic strategy within dietary interventions.