Objective To investigate the effects of different doses of 3,3’-iminodipropionitrile (IDPN) in mice with Tourette syndrome (TS) to optimize the dosage and establish a stable TS model. Methods Thirty-two male C57BL/6J mice were divided randomly into a control group and a model group. The model group was further subdivided and administered low-dose (300 mg/kg), medium-dose (350 mg/kg), and high-dose (400 mg/kg) IDPN, respectively, while the control group received an equal volume of saline by intraperitoneal injection for 7 days. Modeling effectiveness was assessed on days 0 and 7 using stereotypy scoring, the number of head and body twitches, and open-field testing. Dopamine and tumor necrosis factor (TNF-α) levels in serum and brain tissue were measured by enzyme-linked immunosorbent assay. The morphology of striatum and hippocampus tissues were observed by hematoxylin/eosin (HE) staining. Results The stereotypy scores indicated successful modeling of TS in the medium- and high-dose groups. Significant behavioral changes in the open-field test were only detected in the highdose IDPN group (P<0.05). Serum dopamine levels were significantly increased (P<0.05) in the model group, and TNF-α levels were significantly elevated in the medium- and high-dose groups (P<0.05), but there was no significant difference in brain-tissue levels (P>0.05). HE staining showed that the neurons and glial cells in the striatum and hippocampus were morphologically normal in the control group, but there were some neurodegenerative changes and a few swollen neuronal cell bodies in the striatum and hippocampus in the model group, and obvious lymphocyte infiltration in the striatum and hippocampus in the high-dose group. Conclusions Through systematic comparison of varying IDPN dosages in establishing a TS model, this study identified 400 mg/kg as the optimal dosage for effective model induction. These findings provide data to support dose optimization in the TS model and offer valuable references for ensuring the smooth progress of early-stage experiments, which could aid the evaluation of the therapeutic effects of subsequent drug interventions.