After an intracerebral hemorrhage (ICH), impaired glymphatic function (GF) can result in neurotoxin buildup in the brain. In this serial MRI imaging study, we investigated the association between impaired GF and post-stroke cognitive impairment (PSCI). The glymphatic system is a waste clearance mechanism in the brain, consisting of the perivascular space (PVS) formed by astroglial end-feet surrounding arteries and veins. Glymphatic dysfunction has been associated with cognitive decline in patients with neurodegenerative diseases. The diffusion tensor imaging along the perivascular space (DTI-ALPS) index is a non-invasive imaging biomarker to monitor GF. The progression of PSCI in patients after ICH has not been well reported. Here, we serially evaluated GF via measuring the DTI-ALPS index and its association with PSCI after ICH. We serially imaged 18 patients with deep ICH at 9.3 ± 9.1 (V1) and 109 ± 28 (V2) days after stroke on a 3T MRI system. Cognitive assessment and stroke severity were obtained via the Montreal Cognitive Assessment (MoCA) and NIHSS, respectively. The DTI-ALPS index was calculated by measuring diffusivity in three regions of interest (ROI) orthogonal to the PVS surrounding the medullary veins. Hematoma (HV) and edema (EV) volumes were measured. The ipsilesional DTI-ALPS index was correlated with MoCA, HV, and NIHSS. The contralesional DTI-ALPS index was used as a control. Normality of all continuous variables was assessed using the Shapiro-Wilk test. As several key variables were non-normally distributed, non-parametric analyses were used, including Wilcoxon signed-rank tests for paired comparisons, Mann-Whitney U tests for group comparisons, and partial Spearman rank correlations (rS) to examine associations between the DTI-ALPS index and clinical or volumetric measures while adjusting for age and hematoma volume. We enrolled 12 M/6F with an average age of 49 ± 13y. The ipsilesional DTI-ALPS index was significantly lower than the contralesional DTI-ALPS index (p = 0.041) at V2. Temporally, NIHSS (median [IQR] 8.5 [1.0-13.8] to 2.5 [1.0-4.0], p = 0.002), HV (5.03 [3.31-12.62] to 1.28 [0.80-2.73] mL, p < 0.001), and EV (20.34 [9.62-35.44] to 1.09 [0.41-4.79] mL, p < 0.001) were significantly decreased. After adjustment for age and hematoma volume using partial Spearman correlation, the ipsilesional DTI-ALPS index showed a near-significant negative association with NIHSS (partial rS = - 0.48, p = 0.057) and a positive but non-significant association with MoCA (partial rS = 0.28, p = 0.301) at V2. Our finding demonstrated that the DTI-ALPS index is a feasible imaging biomarker for assessing glymphatic dysfunction and it is positively associated with cognitive impairment following intracerebral hemorrhage.