Orally administered baicalein-decorated zinc phosphates (ZnBM) were engineered for mucosal barrier improvement and intestinal inflammation relief. ZnBM with a size of 1.78 μm comprised 5.58 wt% baicalein and 13.17 wt% zinc. The incorporation of baicalein endowed ZnBM with excellent radical scavenging activities. ZnBM exhibited good stability with negligible zinc release in PBS solution for 2 days, and 32.82% of the zinc could reach the gut. In addition, ZnBM polarized macrophages into the anti-inflammatory M2 type and effectively scavenged intracellular reactive oxygen species (ROS) of lipopolysaccharide (LPS)-treated RAW264.7. Meanwhile, ZnBM effectively scavenged intracellular ROS of phorbol 12-myristate 13-acetate (PMA)-induced Caco-2 cells and exerted a reparative effect on the LPS-damaged Caco-2 monolayer, causing an obvious improvement of the barrier function. Reduced systemic exposure to FITC-dextran was observed to illustrate barrier restoration by ZnBM, which was achieved through upregulation of tight junction protein expression. Notably, the commonly used clinical drug 5-aminosalicylic acid is toxic to the liver and kidneys, and commercial ZnO caused the death of mice during treatment. Apparently, the therapeutic effect of ZnBM was significantly better than that of baicalein alone in chronic colitis. Overall, ZnBM exhibited outstanding therapeutic efficacy and is expected to treat colitis due to its effectiveness, biosecurity, facile preparation, and easy storage.