Objective To analyze the causal relationship between cerebrospinal fluid (CSF) metabolites and tic disorder (TD) based on two-sample Mendelian randomization (MR). Methods CSF metabolites data from humans were downloaded from genome-wide association study databases, and CSF metabolites were selected as exposure factors. single nucleotide polymorphisms (SNPs) strongly associated with the exposure factors and independent of each other were selected as instrumental variables. The TD dataset from the Finngen database was downloaded, including 365 cases of TD and 411 816 controls. Analysis was conducted using inverse variance weighting, MR-Egger, weighted median, weighted mode, and simple mode. Sensitivity analysis was conducted using leave-one-out, and multiple-effects testing was conducted using MR-Egger and MR-PRESSO. Heterogeneity was detected using Cochran’s Q. Results A total of 9 CSF metabolites were found to have a causal relationship with the occurrence and development of TD (P<0.05), with a total of 394 SNPs included in the analysis. Inverse variance weighting results showed that N-acetylneuraminic acid [odds ratio (OR)=2.715, 95% confidence interval (CI) (1.102, 6.961), P=0.030], γ-glutamylglutamine [OR=1.402, 95%CI (1.053, 1.868), P=0.021], lysine [OR=2.816, 95%CI (1.084, 7.319), P=0.034] could increase the risk of TD. Cysteinylglycine disulfide [OR=0.437, 95%CI (0.216, 0.885), P=0.021], propionylcarnitine [OR=0.762, 95%CI (0.616, 0.941), P=0.012], pantothenate [OR=0.706, 95%CI (0.523, 0.952), P=0.023], gulareic acid [OR=0.758, 95%CI (0.579, 0.992), P=0.044], and cysteine-glycine [OR=0.799, 95%CI (0.684, 0.934), P=0.005] could reduce the risk of TD. The results of leave-one-out sensitivity analysis were stable, and no horizontal pleiotropy or heterogeneity was observed. Conclusions N-acetylneuraminic acid, γ-glutamylglutamine, and lysine can increase the risk of TD, but cysteinylglycine disulfide, propionylcarnitine, pantothenate, gulagic acid and cysteine-glycine can reduce the risk of TD. However, the mechanism of their effects on TD still needs to be further explored.