Neuroprotection involves preserving the integrity and function of neurons against damage resulting from injuries or neurodegenerative conditions. Diseases such as Alzheimer’s, Parkinson’s, Huntington’s, and amyotrophic lateral sclerosis affect millions of individuals worldwide, with aging recognized as the leading risk factor. Each disorder impacts specific neuronal populations or brain regions and is marked by unique molecular and pathological hallmarks. To unravel the underlying mechanism and identify effective treatments, researchers have developed and employed a variety of disease specific models in both in vitro and in vivo settings. In recent decades, therapeutic development has largely concentrated on addressing factors such as oxidative stress, protein aggregation, neuroinflammation, and disruptions in neurotransmitter systems particularly involving dopamine and acetylcholine. This chapter highlights key examples of neuroprotective agents derived from plants, focusing on their structural categories and modes of action. Many of these natural compounds exhibit promise as therapeutic candidates due to their ability to influence multiple critical signaling pathways, including AMPK, ERK1/2, Akt, and JNK, which are essential to neuronal survival and function.