An imbalance between the production of reactive oxygen species and their neutralization lies at the core of oxidative stress implicated in ischemic stroke (IS) and the subsequent brain tissue damage. The aim of this study was to investigate the effects of common polymorphic variants of the glutamate cysteine ligase catalytic subunit gene on the extent of brain damage and clinical manifestations in patients with ischemic stroke. A total of 589 ischemic stroke survivors were genotyped for 6 single nucleotide polymorphisms (SNPs) of the GCLC gene, including rs12524494, rs17883901, rs606548, rs636933, rs648595 and rs761142, using a MassARRAY-4 analyzer. The study found that genotypes rs636933-G/A-A/A (р = 0.009) and rs761142-A/C-C/C (р = 0.015) were associated with an enlargement of the cerebral lesion size. Genotypes rs12524494-G/G (р = 0.05) and rs606548-T/T (р = 0.003) were associated with a risk of 2 or more IS episodes. Genotype rs17883901-G/A was associated with early onset of IS (р = 0.004). The study revealed multiple associations of GCLC SNPs with the clinical manifestations of ischemic stroke. Thus, GCLC polymorphisms are important DNA markers affecting the size of the cerebral lesion in patients with ischemic stroke and are associated with age at onset, the number of past strokes and the clinical manifestations of the disease.