The present invention provides neuroprotective polyphenol compounds, which can be synthetic analogs of fisetin, baicalein or chlorogenic acid, that maintain neuroprotective, anti-inflammatory, glutathione promoting, and / or antioxidant properties. The neuroprotective polyphenol compounds are useful for promoting, enhancing and / or increasing neuron protection, growth and / or regeneration. The polyphenol compounds further find use for increasing and or maintaining intracellular glutathione (GSH) levels. The polyphenol compounds are also useful for treating, preventing, mitigating and / or delaying neurodegenerative conditions, including diabetes, Parkinson's disease, Huntington's disease, Alzheimer's disease, non-Alzherimer's dementias, multiple sclerosis, traumatic brain injury, spinal cord injury or ALS.