Improving pain management and physical function remains a significant challenge for patients affected by end-stage renal disease (ESRD) undergoing hemodialysis. Non-pharmacological interventions, such as transcranial direct current stimulation (tDCS), have gained attention for their potential to alleviate pain and improve functional outcomes. This study explored the effects of tDCS on pain, fatigue, and functional performance in patients affected by ESRD undergoing hemodialysis and experiencing chronic pain. Thirty-four participants were randomized to receive either active or sham tDCS, with 15 sessions administered over five weeks. Anodal tDCS over C3 with an intensity of 2 mA was administered in 15 sessions, 3 times per week. Visual Analogue Scale for pain (VAS), fatigue, functional performance (sit-to-stand test, stationary walk, timed up and go test (TUG), elbow flexion test, and manual dynamometry) were assessed. We found a significant difference in VAS (p < 0.001) between groups and across time (fifteenth session p < 0.001; at the first, p < 0.001; and second follow-up, p < 0.001). TUG showed significant differences between-group analysis (p = 0.009). No significant differences between groups were observed for fatigue (p = 0.21) and all others functional tests. These findings suggest that tDCS may be a promising, non-invasive intervention for managing pain and improving mobility in patients affected by ESRD undergoing hemodialysis. Future studies with larger samples and extended follow-ups are warranted to further validate these findings and explore the long-term benefits of tDCS. Trial registration: The study is registered on the Brazilian Clinical Trials Registry (ID: RBR-7kym6v8).