Objective: The cause of ulcerative colitis (UC) is unknown, and the use of anti-inflammatory and immunosuppressive drugs with certain side effects is currently replacing treatment. Therefore, it is important to find new healthy foods or ingredients that exhibit potential protective and anti-inflammatory effects on UC. This study investigated the potential protective effect of doenjang on dextran sulfate sodium (DSS)-induced colitis in a mouse model. Materials and methods: Four doenjang samples (TCD21-51-1, TCD21-55-1, TMD21-16-1, and TFD21-1-1) were used. To examine the effects of the four doenjang samples on UC caused by DSS in a mouse model, the clinical symptoms of UC, such as body weight, disease activity index (DAI), and colon macroscopic damage index (CMDI) were analyzed. Moreover, immune-related blood cell counts, serum levels and protein expression of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6), and nitric oxide (NO) production were measured in DSS-induced UC in mice for analysis. Results: The four doenjang samples increased the colon length shortened by DSS, reduced DAI (diarrhea and hemoccult), CMDI (ulceration, inflammation, and hemorrhage) and the content of immune-related cells in the blood. Moreover, the levels of TNF-α, IL-6, and NO increased by DSS were decreased by doenjang, and tissue damage was significantly reduced. Conclusions: These findings confirmed that doenjang exerts protective effects against UC, suggesting its possible use in developing therapeutic strategies or functional products.