Maqui berry (Aristotelia chilensis) is an edible berry. The study aimed to explore the therapeutic effect of maqui berry on inflammatory bowel disease. Maqui berry water extract was separated by multiple solvents extraction. The chemical bases, antioxidant and anti-inflammatory properties of different extract fractions were then compared. Dextran sodium sulfate (DSS)-induced ulcerative colitis mice were used for the pharmacological activity test in vivo. Experimental results showed that the ethyl acetate fraction of maqui berry water extract (MWE) was rich in phenols and exhibited good antioxidant and anti-inflammatory activities. MWE considerably reduced the expression of COX2 and IL-6 in LPS-stimulated RAW 264.7 cells. Inflammatory bowel disease index, MDA, NO, i-NOS, and COX2 in colon tissues and MPO, TNF-α, and IL-1β in blood serums were remarkably decreased in the treatment group compared to in the model group (p < 0.05). Intestinal histopathological damage was significantly alleviated in the treatment group, and the expression of occludin was increased (p < 0.05). MWE treatment alleviated the imbalance of gut microbiota caused by DSS injury. Overall, MWE plays a therapeutic role in ulcerative colitis through its anti-inflammatory effect, reduces immune stress, and regulates gut microbiota.