Neurodegenerative disorders, Alzheimer, Parkinson, Huntington, among others form an array of conditions characterized by loss of neurons, cognitive impairment and motor loss, and are progressive conditions associated with a grave social, economic, and healthcare burden to society. The existing pharmacological treatment affects the progress of the disease much less as it is mainly symptomatic; it causes some interest in alternative treatment methods. Flavonoid, alkaloid, terpenoid, and phenolic compounds, which represent plant secondary metabolites (PSMs) neuroprotective potential, have demonstrated significant neuroprotective effects in preclinical animal models through targeting several pathological mechanisms. These substances reduce oxidative stress by potentiating endogenous antioxidant protection, inhibit neuroinflammation via cytokine and microglial adjustment and prevent toxic protein formation, augment neurotransmitter channels, which maintain the neurotransmitter balance in the neurons further enhancing cognitive and motor functions. The translation of preclinical evidence to a direct clinical application is hampered, however, by limitations in bioavailability, blood-brain barrier penetration, heterogeneity of experiments, and lack of long-term studies, despite the promising results evident in past studies. Delivery optimization, animal models routines, and examination of chronic or combinatorial intervention are critical to bring PSMs to safe and viable therapeutic use in human NDs.