Modern therapeutics have substantially advanced for autoimmune disease treatment, however, these drugs are often associated with substantial adverse effects and safety concerns. Thus, there is considerable interest in the development of new treatment strategies. In the present study, apoptotic bodies derived from neutrophil-like cells (Neu-ABs) were employed as a novel modality for autoimmune disease treatment. Neu-ABs were enriched in immunomodulatory protein associated with the polarization of M2 macrophages, which were taken up by macrophages. Efferocytosis of Neu-ABs induced the polarization of macrophages toward the M2 phenotype and increased the secretion of anti-inflammatory mediators in vitro. In collagen-induced arthritis and dextran sulfate sodium-induced ulcerative colitis mouse models, Neu-ABs accumulated in the inflamed tissues. The macrophages in the inflamed tissues phagocytose the Neu-ABs and then exhibit a cascade of anti-inflammatory events via macrophage phenotype regulation in vivo. The therapeutic efficiency of Neu-ABs for rheumatoid arthritis and ulcerative colitis was comparable to their corresponding clinical medication. Still, Neu-ABs exhibited good biological safety. These findings indicate a polarization effect of Neu-ABs for macrophages and highlight the potential of Neu-ABs for autoimmune disease treatment.