Overall, our results indicated that C. butyricum‐GLP‐1 could secrete GLP‐1, cross the blood–brain barrier into the brain, and act on the GLP‐1R to activate the mitophagy pathway, thus exerting its neuroprotective effects against PD, and could enhance the intestinal mucosal barrier by rectifying the dysbiosis in the gastrointestinal tract, which contributed to the improvement of PD. The gene discussed is GLP1R; the disease is Parkinson disease.