Aim/Background: Parkinson's Disease (PD), the loss of dopaminergic neurons in the substantial nigra part of the brain leading to neurodegeneration. Materials and Methods: The objective of this study was to observe the neuroprotective effect of the synthesized derivatives in 6-hydroxydopamine (6-OHDA) induced rat model. Here, designed naphthalene substituted azetidinone compounds defended the lesions caused by 6-OHDA in rat model for PD. Male wistar rats (250g) were subjected into sham operated, controlled 6-OHDA, 6-OHDA treated L-dopa (Levodopa) and lesioned 6-OHDA with azetidinone derivatives (30mg/kg) where oxidative stress and behavioral characteristic were observed. Results: Induced synthesized derivatives partly have shown the reversed behavioral and neuronal changes compared to 6-OHDA lesioned rats. The free radical scavenging activity for the compound IVc, IVe and IVf were found to be 88, 70, 78 respectively as compared to that of 6-OHDA with L-dopa with 90%. Conclusion: The efficacy of the azetidinone derivatives was found to be promising in providing relief to oxidative stress and the derivatives could be used in the therapeutic approaches in preventing neurodegeneration.