Background <p>Stroke results in substantial long-term disability, necessitating effective recovery interventions. This study explored the effects of multi-channel transcranial direct current stimulation (tDCS) on hemodynamic responses and upper limb motor function in stroke patients, targeting the ipsilesional primary motor cortex (M1) and anterior intraparietal sulcus (aIPS).</p> Methods <p>A double-blind, randomized, sham-controlled trial was conducted with 24 stroke patients (18 men; mean age, 57.3×14.2 years), who underwent 10 sessions of real or sham multi-channel tDCS combined with upper limb exercises. Functional near-infrared spectroscopy (fNIRS) measured resting-state cerebral hemodynamic responses for 5&#xa0;min before and after each session. Motor function was evaluated using the Fugl–Meyer assessment for upper extremity (FMA-UE), box and block test (BBT), and other motor function tests before and after the interventions.</p> Results <p>The real multi-channel tDCS group exhibited increases in regional accumulation of oxyhemoglobin (HbO_Acc) and stronger seeded connectivity networks within the motor cortex poststimulation. In contrast, the sham group exhibited disassociation from these areas. The group × time interaction was significant for the Box and Block Test (BBT), indicating greater improvements in gross manual dexterity in the real-tDCS group compared to the sham group. While poststimulation changes in HbOAcc were examined in relation to FMA-UE scores, no strong linear relationship was observed in the real-tDCS group.</p> Conclusions <p>Multi-channel tDCS targeting the ipsilesional M1 and aIPS, combined with upper limb exercises, showed potential effects on cerebral hemodynamics and motor function in stroke patients. These findings suggest that multi-channel tDCS may have a role in motor rehabilitation, but further research is needed to validate its efficacy and clinical applicability.</p> ClinicalTrials.gov <p>This study was registered at ClinicalTrials.gov (NCT05275114).</p>