Previous observational studies have suggested an association between tryptophan (TRP)-kynurenine (KYN) pathway and inflammatory bowel disease (IBD). However, whether there is a causal relationship among them remains unclear. Therefore, a two-sample Mendelian randomization (MR) study was conducted to explore the potential causal effects of crucial metabolites in TRP-KYN pathway on IBD and its subtypes. Using summary data from genome-wide association studies, a two-sample MR was employed to evaluate the genetic associations between TRP and KYN as exposures and IBD as an outcome. The inverse variance weighted method was used as the primary MR analysis, with MR-Egger, weighted mode, simple mode, and weighted median methods as complementary analyses. The odds ratios (OR) and 95% confidence intervals (CI) were determined for TRP-IBD (OR 0.739, 95% CI [0.697; 0.783]), TRP-UC (OR 0.875, 95% CI [0.814; 0.942]), TRP-CD (OR 0.685, 95% CI [0.613; 0.765]), KYN-IBD (OR 4.406, 95% CI [2.247; 8.641]), KYN-UC (OR 2.578, 95% CI [1.368; 4.858], and KYN-CD (OR 13.516, 95% CI [4.919; 37.134]). Collectively, the MR analysis demonstrated a significant protective association between TRP and IBD, whereas KYN was identified as a risk factor for IBD.© 2024. The Author(s).