Previous observational studies have suggested a potential causal relationship between Helicobacter pylori (H. pylori) infection and immune thrombocytopenia (ITP). However, the evidence for causal inference remains contentious, and the underlying mechanisms require further investigation. To delve deeper into the relationship between H. pylori and ITP, we conducted a Mendelian randomization (MR) analysis. In this study, we used two-sample Mendelian Randomization (MR) to assess the causality of seven different specific protein antibodies targeting H. pylori on ITP. 76 single nucleotide polymorphisms (SNPs) related to H. pylori antibody levels were obtained from the European Bioinformatics Institute (EBI). Summary data on ITP was obtained from the FinnGen database, and inverse variance weighted (IVW) analysis was identified as our main method. The reliability of the findings was ensured by performing many sensitivity analyses. Genetically predicted serum levels of H. pylori GroEL antibodies were positively associated with an increased risk of ITP (odds ratio [OR] = 1.802, 95% CI 1.106-2.936, P = 0.01799). No causal relationship was found between other H. pylori antibodies and ITP. The outcomes derived from our two-sample Mendelian randomization analysis demonstrate a discernible link between the levels of H. pylori GroEL antibodies and an augmented susceptibility to ITP. However, it is imperative to expand the sample size further in order to corroborate the correlation between H. pylori infection and ITP.