Post‐stroke sequelae includes loss functions, such as cognitive and sensory‐motor which lead to emotional and social problems, reducing quality of life and well‐being. The main aim of our study was to investigate the effects of transcranial laser photobiomodulation together with neuromuscular electrical stimulation (NMES) in post‐stroke patients. We performed a clinical trial and an ex vivo study. For the clinical trial, hemiplegic patients were separated into two groups: Treated Group (TG): Hemiplegics treated with transcranial laser (on) associated with NMES (on) and; Placebo Group (PG): Hemiplegics treated with placebo transcranial laser (off) associated with NMES (on). The cluster prototype includes 12 diode laser beams (4 × 660 nm, 4 × 808 nm and 4 × 980 nm) with average power of 720 mW per cluster applied during one minute, leading to 43.2 J energy per cluster. Fifteen regions for all head were irradiated by cluster, leading to 648 J energy per session. The parameters of NMES of the paretic limbs to generate extension wrist and ankle dorsiflexion were symmetrical biphasic rectangular waveforms, 50 Hz frequency, 250 μs pulse duration, and adjustable intensity to maintain the maximum range of motion (amplitude between 0 and 150 mA). Our clinical trial showed improvement of cognitive function, pain relief, greater manual dexterity, enhancement of physical and social–emotional health which lead to better quality of life and well‐being. There was also increased temperature in the treated regions with laser and NMES. For the ex vivo study, the distribution of infrared and red radiation after penetration through the cranium and hemihead of cadavers were showed. Therefore, transcranial laser photobiomodulation associated with NMES can be an important therapeutic resource for rehabilitation after stroke.