Natural bioactive compounds including curcumin, resveratrol, luteolin, quercetin, and catechins demonstrate neuroprotective effects by simultaneously targeting oxidative stress, neuroinflammation, and protein aggregation in neurodegenerative diseases. These molecules modulate critical cellular pathways including NF-κB, MAPK, PI3K/AKT, and Nrf2 while reducing amyloid-beta buildup and protecting dopaminergic neurons in preclinical studies. This multi-pathway approach represents a departure from conventional single-target pharmaceutical interventions that primarily manage symptoms without altering disease progression. The compounds' ability to enhance mitochondrial function and activate autophagy pathways offers particular promise for conditions like Alzheimer's and Parkinson's disease, where cellular energy deficits and waste accumulation drive neuronal death. However, significant barriers remain before clinical application. Poor bioavailability and pharmacokinetic variability plague these natural compounds, limiting their therapeutic potential despite promising laboratory results. The research landscape increasingly recognizes that successful neurodegeneration treatments will likely require combination approaches rather than silver bullets, making these multi-target natural products compelling candidates for future drug development once delivery challenges are resolved.