Ulcerative colitis (UC) is a common inflammatory bowel disease which on prolongation causes colorectal cancer (CRC) making UC as the highest risk factor for CRC development. Despite the use of Aegle marmelos in folk medicine, few studies have reported its colonic healing activity. We exploited the use of dextran sodium sulfate (DSS) in inducing colitis in Swiss albino mice and examine the inflammatory modulating effect of A. marmelos fruit extract (AME). HPLC analysis confirmed the presence of two biologically active compounds namely umbelliferon (a coumarin-derivative) and lupeol (triterpenoid). Fourteen days feeding of DSS to mice elicited colitis, with drastically reduced body weight with altered clinical severity score, combined with shortening of colon length. Oral administration of AME (50mg/kg) evidenced a significant suppression of disease symptoms. The increased mRNA expressions of interleukin (IL) 2, IL-6 and tumor necrosis factor α during colitis, were also reduced significantly. Notable reduction in the NF-κB expression in the colonic region was also noted which is substantiates with docking analysis were UMB and LUP found in AME bounds with NF-κB. Furthermore, DSS-altered histopathological features of colon were also recovered on treatment with AME. Thus the observation revealed the restorative significance of AME in healing the DSS-induced colitis in mice by modulating NF-κB and regulating pro-inflammatory mediators involved in the colonic injury.