Photobiomodulation (PBM) therapy on the brain uses red to near-infrared (NIR) light to treat neurological and psychological disorders. It activates cytochrome c oxidase in mitochondria, enhancing ATP synthesis and triggering calcium ion release, which activates transcription factors and gene expression. This process improves neuronal metabolism, reduces oxidative stress, and promotes neurogenesis and synaptogenesis, showing promise for conditions like dementia, stroke, and Parkinson's disease. However, delivering sufficient light to the brain through transcranial methods is challenging due to limited tissue penetration, prompting exploration of intracranial and intranasal delivery. This review summarizes preclinical and clinical studies on PBM's effects on brain disorders, highlighting its potential as a therapeutic modality. PBM mechanisms include mitochondrial cytochrome c oxidase activation, light-sensitive ion channels, and retrograde mitochondrial signaling. Current delivery methods include transcranial, intracranial, and intranasal approaches, with challenges in light penetration. PBM improves cerebral blood flow, angiogenesis, and reduces oxidative stress and neuroinflammation, offering neuroprotection and anti-apoptotic effects. It also enhances neurogenesis and synaptogenesis, supporting cognitive function. Systemic effects of PBM include neuroprotective impacts on non-brain regions, potentially benefiting the brain. Clinical applications show promise in treating stroke, TBI, Alzheimer's disease, Parkinson's disease, and depression, with potential for cognitive enhancement in healthy individuals. PBM is considered safe with minimal adverse effects, and ongoing research aims to optimize its therapeutic use.Photobiomodulation (PBM) therapy on the brain uses red to near-infrared (NIR) light to treat neurological and psychological disorders. It activates cytochrome c oxidase in mitochondria, enhancing ATP synthesis and triggering calcium ion release, which activates transcription factors and gene expression. This process improves neuronal metabolism, reduces oxidative stress, and promotes neurogenesis and synaptogenesis, showing promise for conditions like dementia, stroke, and Parkinson's disease. However, delivering sufficient light to the brain through transcranial methods is challenging due to limited tissue penetration, prompting exploration of intracranial and intranasal delivery. This review summarizes preclinical and clinical studies on PBM's effects on brain disorders, highlighting its potential as a therapeutic modality. PBM mechanisms include mitochondrial cytochrome c oxidase activation, light-sensitive ion channels, and retrograde mitochondrial signaling. Current delivery methods include transcranial, intracranial, and intranasal approaches, with challenges in light penetration. PBM improves cerebral blood flow, angiogenesis, and reduces oxidative stress and neuroinflammation, offering neuroprotection and anti-apoptotic effects. It also enhances neurogenesis and synaptogenesis, supporting cognitive function. Systemic effects of PBM include neuroprotective impacts on non-brain regions, potentially benefiting the brain. Clinical applications show promise in treating stroke, TBI, Alzheimer's disease, Parkinson's disease, and depression, with potential for cognitive enhancement in healthy individuals. PBM is considered safe with minimal adverse effects, and ongoing research aims to optimize its therapeutic use.