To evaluate the neuroprotective effect of nootropic drugs, piracetam and vincamine, on Parkinsonʹs disease (PD) in rats, forty adult male Wistar albino rats were randomized into five equal groups: control, haloperidol-induced PD group, and PD groups orally given piracetam (300 mg/kg/day), vincamine (20 mg/kg/day) or both. Four weeks later, motor performance was assessed by stepping test. Y-maze, forced swimming and olfactory preference tests were done for cognitive and behavioral evaluation. Blood samples were collected for measuring serum glucose, calcium, creatine phosphokinase (CPK) and glial cell-derived neurotrophic factor (GDNF). Thereafter, rats were sacrificed and brains were dissected. Striatal tissue of left hemisphere was isolated and homogenized for assay of dopamine, malondialdehyde (MDA), nitrite/nitrate, reduced glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD), tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1ß). Right hemisphere was used for histopathological examination of substantia nigra. Results: Rats of PD group showed bradykinesia, cognitive impairment, depressive-like behavior and hyposmia, reductions in serum calcium and GDNF, and in striatal dopamine, GSH, GPx and SOD, while serum glucose and CPK, and striatal MDA, nitrite/nitrate, IL-1ß and TNF-α were increased, as compared to control.Both drugs improved neurological dysfunction and biochemical parameters, as compared to PD group. The histopathological findings revealed neuro-degeneration and neuro-inflammation in PD group, that improved in treated groups. The piracetam effect was mainly anti-inflammatory, while vincamine was mainly antioxidant. Combined treatment resulted in a more potent amelioration of haloperidol-induced changes. Conclusion: Piracetam and vincamine exhibit neuroprotective activity in haloperidol-induced PD, that is more potent with their combination.