Background: Parkinson's disease (PD) is the second most chronic neurodegenerative disorders affecting the age-old peoples worldwide. Therefore, in the present study, we assessed the neuroprotective effect of neferine against the progressive Parkinson's induced mouse model. Mice were induced PD by treating them with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a neurotoxin selectively disrupts the dopaminergic neurons and then treated with neferine, a plant alkaloid. Materials and Methods: The neuroprotectant effect of neferine against MPTP-induced Parkinson's was assessed with behavioral analysis such as grid test and stride length measurement test, and the motor coordination was confirmed with rota rod test. Further, to assess the anti-inflammatory property of neferine, the levels of pro-inflammatory cytokines tumor necrosis factor-α, interleukin (IL)-1β and IL-6 were estimated. Results: To confirm the neuroprotectant effect of neferine, the levels of dopamine and the protein expression of inducible nitric oxide synthase, cylcooxygenase-2, rate-limiting enzyme of dopamine synthesis tyrosine hydroxylase in the substantia nigra tissue of control and experimental mice were evaluated. Our overall results authentically prove that neferine acts an anti-inflammatory agent decreased the levels of pro-inflammatory cytokines and increased the dopamine levels in substantia nigra, thereby protecting the mice from MPTP-induced Parkinsonism. Conclusion: The behavioral analysis also confirmed neferine as a persuasive neuroprotectant with nil side effects and can be prescribed as a drug to treat Parkinson's with subject to further trials.