Abstract The gastrointestinal tract is not only an important component of the digestive system but also a crucial part of the body’s immune system. Numerous studies have reported that gastrointestinal immunity plays a critical role in many extraintestinal diseases, including neurodegenerative disorders. However, the relationship between gastric mucosal immunity and neurodegenerative diseases, such as Parkinson’s disease(PD), remains underexplored. The rate of H. pylori infection was assessed using the 13 C-Urea Breath Test (13 C-UBT) in a case-control study involving 315 PD patients and a control group of 22,383 outpatients. Multivariate regression and propensity score matching (PSM) analyses were employed to adjust for confounding factors. A lower H. pylori infection rate was found in PD cases compared to outpatient controls (DOB ≥ 8, 22.5% versus 27.5%, p = 0.049; DOB ≥ 4, 28.6% versus 33.9%, p = 0.046). After adjusting for confounding factors, the H. pylori infection rate remained lower in PD cases compared to controls. The study revealed an inverse correlation between H. pylori infection and PD, suggesting that H. pylori infection could potentially act as a protective factor against the development of PD.