Parkinson's Disease (PD), is defined as a neurodegenerative disorder that leads to the death of dopamine neuron found in the substantia nigra (SN) in the brain, resulting in movement disorders. Accordingly, current treatment strategies for PD have targeted the dopamine system. However, There is an urgent need for finding effective treatments to improve the progression of the disease and improve the quality of life; however, existing therapies can neither slow nor prevent the progression of PD. The disease is caused by a lack of dopamine (DA), so the primary therapy involves DA replacement drugs. In this paper, the effectiveness of sitagliptin and liraglutide, will be investigated both of which have Food and Drug administration's (FDA) approval for treating type II diabetes. Aim:This study aims to investigate the extent to which Sitagliptin and Liraglutide are effective on lipopolysaccharide (LPS) rodent model of parkinson's disease. LPS is an endotoxin that is extracted from gram negative bacteria; as such, it functions as a potent stimulator of microglia, and researchers have used it to examine the inflammatory process of the pathogenesis of the disease. Thus, LPS can replicate two main characteristics of PD: microglia's extensive activation as well as the loss of nigrostriatal dopaminergic neurons. Method: Twenty four Male rats, weighing between (250-300) g, were randomized then divided into 4 different groups of 6 rats each. Group A was the control group, group B rats were subjected to LPS alone (intracerebral injection), and group C was subjected to LPS + (s.c) Liraglutide for 14 days after intracerebral injection of LPS. Finally group D where LPS + oral Sitagliptin for 14 days after intracerebral injection of LPS. This study assessed the LPS induced lesion severity both behaviorally and neurochemically. Result: Fourteen days after LPS intracerebral injection of LPS, and following an apomorphine challenge, LPS lesioned rats receiving Liraglutide or Sitagliptin showed significantly lower tight contralateral circling in comparison to LPS only group. Consistent with these findings, concentrations of the striatal tissue dopamine were significantly higher in groups C and D (LPS + Liraglutide or Sitagliptin treated rats) versus group B (LPS only group). Conclusion: This study showed that Liraglutide and Sitagliptin are neuroprotective compounds that can slow and protect dopaminergic neurons and they have the capacity to alleviate the pathophysiology of Parkinson's disease (PD) because of they might to reduced the inflammatory prosses.