For inflammatory bowel disease (IBD) therapy, systemic exposure of anti-TNF-α antibodies brought by current clinical injection always causes serious adverse effects. Colon-targeted delivery of anti-TNF-α antibodies through the oral route is of great importance but remains a formidable challenge. Here, we reported a biomimetic nanocomposite made of a ginger-derived exosome and an inorganic framework for this purpose. A large mesoporous silicon nanoparticle (LMSN) was uniquely customized for the antibody (infliximab, INF) to load it at high levels up to 61.3 wt% and prevent its aggregation. Exosome-like nanovesicles were isolated from ginger (GE) with a high-level production (17.5 mg kg-1). Then, ultrasound was used to coat GE onto the LMSN to obtain the biomimetic nanocomposite LMSN@GE. As expected, LMSN@GE showed advantages in the oral delivery of INF: stability in the gastrointestinal tract, colon-targeted delivery and high intestinal epithelium permeability. Amazingly, GE also presented an anti-inflammatory effect by blocking the NLRP3 inflammasome in addition to its delivery value. As a result, INF/LMSN@GE showed a significantly higher efficacy in colitis mice compared to the intravenously administered INF. This work provides new insights into colon-targeted delivery of anti-TNF-α antibodies via the oral route. Moreover, it puts forward a novel strategy for drug delivery using one therapeutic agent (herb-derived exosomes).