The present study investigates the anti-parkinsonian activity of various extracts of Justicia gendarussa (JG) leaves in MPTP-induced neurotoxicity mice. Parkinson's disease (PD) is a neurodegenerative syndrome belongs to a group of motor symptoms disorders. In PD, brain cells degenerated in some parts of the brain which produce dopamine. JG herb is widely distributed in tropical regions of the world. The various parts of the plant are employed traditionally in the treating of various disorders. The present study was designed with 11 group's mice with 6 each. Group 1 (control), Group 2 (MPTP 20 mg/kg IP four injections at 2 h intervals), Group 3 (L-dopa), and Group 4 to Group11 were administered with Ethanol, Ethyl acetate, Aqueous and n-hexane extracts for 7 days with dose 200 and 400 mg/kg orally along with MPTP 4 injections on day 1. After 7 days, Neurotransmitters, in vivo antioxidant levels, histopathology observation, and isolation of Phytoconstituents by column and characterization studies were performed. The results of the study showed that significant alterations in neurotransmitter levels increased Malondialdehyde (MDA) and decreased reduced glutathione levels and degeneration of neurons. All the neurotransmitters and reduced glutathione levels were remarkably (P<0.001) and dose-dependently restored, and MDA levels were decreased with different extracts of JG at selected doses. The effective neuroprotective activity was observed with ethanol extract at 400 mg/kg, isolation of ethanol extract showed the presence of naringenin, Isoflavone. Neuroprotective activity of JG leaves could be due to the presence of isolated compounds and other L-dopa-like constituents; hence JG extracts has a prominent neuroprotective effect in PD.