Oral medication for ulcerative colitis (UC) is often hindered by challenges such as inadequate accumulation, limited penetration of mucus barriers, and the intricate task of mitigating excessive ROS and inflammatory cytokines. Here, we present a strategy involving sodium alginate microspheres (SAMs) incorporating M2 macrophage membrane (M2M)-coated Janus nanomotors (denominated as Motor@M2M) for targeted treatment of UC. SAM provides a protective barrier, ensuring that Motor@M2M withstands the harsh gastric milieu and exhibits controlled release. M2M enhances the targeting precision of nanomotors to inflammatory tissues and acts as a decoy for the neutralization of inflammatory cytokines. Catalytic decomposition of H2O2 by MnO2 in the oxidative microenvironment generates O2 bubbles, propelling Motor@M2M across the mucus barrier into inflamed colon tissues. Upon oral administration, Motor@M2M@SAM notably ameliorated UC severity, including inflammation mitigation, ROS scavenging, macrophage reprogramming, and restoration of the intestinal barrier and microbiota. Consequently, our investigation introduces a promising oral microsphere formulation of macrophage-biomimetic nanorobots, providing a promising approach for UC treatment.