Neurological ailments, including stroke, Alzheimer’s disease (AD), epilepsy, Parkinson’s disease (PD), and other related diseases, have affected around 1 billion people globally to date. PD stands second among the common neurodegenerative diseases caused as a result of dopaminergic neuron loss in the midbrain’s substantia nigra regions. It affects cognitive and motor activities, resulting in tremors during rest, slow movement, and muscle stiffness. There are various traditional approaches for the management of PD, but they provide only symptomatic relief. Thus, a survey for finding new biomolecules or substances exhibiting the therapeutic potential to patients with PD is the main focus of present-day research. Medicinal plants, herbal formulations, and natural bioactive molecules have been gaining much more attention in recent years as synthetic molecules orchestrate a number of undesired effects. Several in vitro, in vivo, and in silico studies in the recent past have demonstrated the therapeutic potential of medicinal plants, herbal formulations, and plant-based bioactives. Among the plant-based bioactives, polyphenols, terpenes, and alkaloids are of particular interest due to their potent anti-inflammatory, antioxidant, and brain-health-promoting properties. Further, there are no concise, elaborated articles comprising updated mechanism-of-action-based reviews of the published literature on potent, recently investigated (2019–2023) medicinal plants, herbal formulations, and plant based-bioactive molecules, including polyphenols, terpenes, and alkaloids, as a method for the management of PD. Therefore, we designed the current review to provide an illustration of the efficacious role of various medicinal plants, herbal formulations, and bioactives (polyphenols, terpenes, and alkaloids) that can become potential therapeutics against PD with greater specificity, target approachability, bioavailability, and safety to the host. This information can be further utilized in the future to develop several value-added formulations and nutraceutical products to achieve the desired safety and efficacy for the management of PD.

The traditional neuron-centric model of brain disorders has attributed neurodegeneration primarily to intrinsic neuronal pathologies such as protein aggregation and synaptic failure in Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease, and amyotrophic lateral sclerosis, and has often been extended to other CNS conditions such as multiple sclerosis, traumatic brain injury, and autism spectrum disorder. However, accumulating evidence highlights glial cells—microglia, astrocytes, and oligodendrocytes—as central drivers of neuroinflammation and disease progression, fundamentally revising this view. Microglia, the brain’s resident immune cells, rapidly sense pathological signals such as amyloid-β and α-synuclein through pattern-recognition receptors (e.g., TLR4) and inflammasome signaling (e.g., NLRP3). This sensing induces a shift from homeostatic surveillance to disease-associated pro-inflammatory states marked by increased release of cytokines such as tumor necrosis factor-alpha, IL-1β, and IL-6. Activated microglia, in turn, can promote reactive astrocytosis, characterized by elevated GFAP and complement C3, which may impair amyloid clearance, disrupt the blood–brain barrier, and contribute to neurotoxicity through reactive oxygen species and glutamate dysregulation. Sustained crosstalk among glial cells via extracellular vesicles and connexin-mediated signaling can amplify inflammation and counter-regulatory neuronal signals. In AD, early protective microglial phagocytosis gives way to plaque-associated dysfunction, accelerating tau pathology and synaptic loss, whereas in PD, α-synuclein-induced glial activation can promote inflammasome-dependent pyroptosis and dopaminergic neuron degeneration. Similar glia-driven inflammatory cycles contribute to other neurodegenerative disorders and may link disease progression to gut–brain–immune interactions. Therapeutic strategies targeting glial polarization, particularly inhibition of the NLRP3 inflammasome, offer promise by restoring neuroprotective functions without broad immunosuppression. This review emphasizes the dual roles of glia and supports integrated neuro-glial models for precision therapies in brain disorders.