Neurodegeneration is the progressive loss of neuronal structures and functions that lead to copious disorders like Alzheimer's (AD), Parkinson's (PD), Huntington's (HD), amyotrophic lateral sclerosis (ALS), and other less recurring diseases. Aging is the prime culprit for most neurodegenerative events. Moreover, the shared pathogenic factors of many neurodegenerative processes are inflammatory responses and oxidative stress (OS). Unfortunately, it is very complicated to treat neurodegeneration and there is no effective remedy. The rapid progression of the neurodegenerative diseases that exacerbate the burden and the concurrent absence of effective treatment strategies force the researchers to investigate more therapeutic approaches that ultimately target the causative factors of the neurodegeneration. Phytochemicals have great potential to exert their neuroprotective effects by targeting various mechanisms, such as OS, neuroinflammation, abnormal protein aggregation, neurotrophic factor deficiency, disruption in mitochondrial function, and apoptosis. Therefore, this review represents the molecular mechanisms of neuroprotection by multifunctional phytochemicals to combat age-linked neurodegenerative disorders. Display omitted •Phytochemicals activate PI3K/Akt, PKC, ERK1/2 signaling pathways to affect synaptic plasticity and memory formation.•Phytochemicals regulate the expression of antioxidant enzymes by activation of the Keep1/Nrf2/ARE pathway.•Phytochemicals control the secretases activity of the APP processing pathway and prevent the formation of neurotoxic Aβ.•Phytochemicals block mTOR activity and promote autophagic clearance of pathogenic proteins.•Phytochemicals enhance the activity of ETC and block the mitochondrial membrane permeability