Oxidative stress plays a major role in pathogenesis of atherosclerosis which is responsible for stroke. Glutathione S-transferases (GSTs) detoxify metabolites produced by oxidative stress within the cell and protect the cells against injury. This study aimed to investigate the association of polymorphisms in GSTT1, GSTM1 genes and GST activity with ischemic stroke risk. Patients had almost the same GST activity as that of controls. No significant differences were found between patients and controls in terms of GSTT1 null, GSTM1 null and GSTT1/GSTM1 double null genotype frequencies. Besides, both patients and controls with double GSTT1/GSTM1 null genotypes had the lowest serum GST activities. Compared to the present genotypes, GSTT1 null (OR = 4.888; P = 0.006) and GSTM1 null (OR = 2.383; P = 0.011) genotype groups contained relatively more hypertensive stroke patients. This study showed that GSTT1 and GSTM1 null genotypes, together with hypertension, may play a significant role in the pathogenesis of ischemic stroke.