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A growing body of evidence has suggested that the imbalance of epigenetic markers and oxidative stress appears to be involved in thepathophysiology and progression of stroke. Thus, strategies that modulate these biomarkers might be considered targets for neuroprotection and novel therapeutic opportunities for these patients. Physical exercise has been reported to induce changes in these epigenetic markersand improve clinical outcomes in different populations. However, little is reported on this in post-stroke patients. The purpose of this study was to investigate the effect of a single exercise session with WalkAide functional electrical stimulation (FES) on cognitive performance,clinical functional parameters, oxidative stress and epigenetic modulation in post-stroke individuals. In this crossover design study, 12post-stroke individuals aged 54–72 years of either sexes were included and subjected to a single session of exercise (45 minutes) withoutWalkAide functional electrical stimulation (EXE alone group), followed by another single session of exercise (45 minutes) with WalkAidefunctional electrical stimulation (EXE + FES group). The clinical functional outcome measures, cognitive performance and blood collections for biomarker measurements were assessed pre- and post-intervention. After intervention, higher Berg Balance Scale scores were obtained in the EXE + FES group than in the EXE alone group. There was no significant difference in the Timed Up and Go test results post-intervention between EXE alone and EXE + FES groups. After intervention, a better cognitive performance was found in both groups compared withbefore the intervention. After intervention, the Timed Up and Go test scores were higher in the EXE + FES group than in the EXE alone group. In addition, the intervention induced lower levels of lipid peroxidation. After intervention, carbonyl level was lower, superoxide dismutaseactivity and superoxide dismutase/catalase activity ratio were higher in the EXE + FES group, compared with the EXE group alone. In eachgroup, both histone deacetylase (HDAC2) and histone acetyltransferase activities were increased after intervention compared with beforethe intervention. These findings suggest that a single exercise session with WalkAide FES is more effective on balance ability and cognitiveperformance compared with conventional exercise alone in post-stroke patients. This is likely to be related to the regulation of oxidative stress markers. The present study was approved by the Research Ethics Committee of the Methodist University Center-IPA (approval No. 2.423.376) on December 7, 2017 and registered in the Brazilian Registry of Clinical Trials—ReBEC (RBR-9phj2q) on February 11, 2019.