Lesions in the basal ganglia present different neuroimaging manifestations compared to other regions. The functional connectivity and white matter (WM) microstructural alterations in patients with left basal ganglia acute ischemic stroke (AIS) remain unknown. This study aimed to explore the alterations of functional connectivity and WM microstructure, as well as their relationship with cognitive performance in patients with left basal ganglia AIS. We acquired resting-state functional MRI (rs-fMRI) and diffusion kurtosis imaging (DKI) data from 41 individuals with left basal ganglia AIS and 41 healthy controls (HC). The degree centrality (DC) method was applied to calculate the functional connectivity and Tract-Based Spatial Statistics was employed to evaluate the voxel-based group differences of diffusion metrics for the values of fractional anisotropy (FA), mean diffusivity, axial diffusivity (AD), radial diffusivity, mean kurtosis (MK), axial kurtosis, and radial kurtosis (RK). AIS showed attenuated DC in the bilateral precuneus and enhanced DC in the left caudate nucleus, compared with HC. In AIS, DC in the left caudate nucleus correlated positively with the Montreal Cognitive Assessment (MoCA) score (r = 0.681, p <
0.05). AIS had significantly decreased FA, AD, MK, and RK in WM tracts, including the internal capsule (IC), genu of corpus callosum (CC), body of CC, left superior longitudinal fasciculus (SLF), left cerebral peduncle, left corticospinal tract, anterior corona radiata (ACR), and left cingulum gyrus (CG). The MK in a cluster including the body of CC, right IC, left cingulate, SLF, ACR, and left CG was also significantly negatively correlated with MoCA scores (r = -0.508, p <
0.05). This study revealed that left basal ganglia AIS not only disrupted the functional connectivity of the whole brain but also had a pervasive impact on the WM microstructure of the whole brain. These findings provide novel insights into the underlying neural mechanisms of early cognitive decline in patients after AIS.