PURPOSE: This study examined the topological properties of brain white matter networks in overt hypothyroidism (OH) patients and their links to cognitive and emotional dysfunction. MATERIALS AND METHODS: Fifty OH patients and 92 healthy controls underwent brain magnetic resonance imaging, clinical assessments and neuropsychological evaluations. Graph-theoretical network analysis based on diffusion tensor imaging was used to calculate global and local topological properties. Between-group differences were analyzed, and partial correlation and mediation analyses were conducted to explore relationships among topological metrics, clinical variables and neuropsychological scores. RESULTS: The OH group showed significantly higher depressive and anxious scores, and lower cognitive scores. In the global topological analysis, the OH group showed decreased global efficiency, which was negatively correlated with the Hamilton Rating Scale for Depression-24 scores. Local topological abnormalities were predominantly observed in the nodal efficiency (NE), degree centrality and nodal local efficiency of several regions within the limbic system and default mode networks. Notably, NE in the left amygdala and left paracentral lobule was negatively correlated with the Hamilton Rating Scale for Depression-24 scores, and decreased NE in the right median cingulate and paracingulate gyri was positively correlated with executive function/visuospatial ability scores and the clock drawing test score. CONCLUSION: OH patients show depression, anxiety and cognitive impairments linked to global efficiency and regional abnormalities in the limbic system and default mode network. These findings provide insights into the neuropathophysiological mechanisms underlying emotional and cognitive impairments.