Introduction: End-stage renal disease (ESRD) typically causes changes in brain structure, and patients with ESRD often experience cognitive and sleep disorders. We aimed to assess the changes in the subcortical structure of patients with ESRD and how they are associated with cognitive and sleep disorders.Methods: We involved 36 adult patients for maintenance hemodialysis and 35 age- and gender-matched control individuals. All participants underwent neuropsychological examination and 3T magnetic resonance imaging (MRI) to acquire T1 anatomical images. The laboratory blood tests were performed in all patients with ESRD close to the time of the MR examination. We used volumetric and vertex-wise shape analysis approaches to investigate the volumes of 14 subcortical structural (e.g., bilateral accumbens, amygdala, hippocampus, caudate, globus pallidus, putamen, and thalamus) abnormalities in the two groups. Analyses of partial correlations and shape correlations were performed in order to identify the associations between subcortical structure, cognition, and sleep quality in patients with ESRD.Results: The volumetric analysis showed that compared with the healthy control group, patients with ESRD had less bilateral thalamus (left: p < 0.001; right: p < 0.001), bilateral accumbens (left: p < 0.001; right: p = 0.001), and right amygdala (p = 0.002) volumes. In the vertex-wise shape analysis, patients with ESRD had abnormal regional surface atrophy in the bilateral thalamus, right accumbens, left putamen, and bilateral caudate. Moreover, the Montreal Cognitive Assessment (MoCA) score was associated with volume reduction in the bilateral thalamus (left: Spearman ρ = 0.427, p = 0.009; right: ρ = 0.319, p = 0.018), and the Pittsburgh Sleep Quality Index (PSQI) score was associated with volume reduction in the bilateral accumbens (left: ρ = −0.546, p = 0.001; right: ρ = −0.544, p = 0.001). In vertex-wise shape correlation analysis, there was a positive significant correlation between regional shape deformations on the bilateral thalamus and MoCA score in patients with ESRD.Conclusion: Our study suggested that patients with ESRD have subcortical structural atrophy, which is related to impaired cognitive performance and sleep disturbances. These findings may help to further understand the underlying neural mechanisms of brain changes in patients with ESRD.