Parkinson's disease (PD) is second only to Alzheimer's disease as the most common and debilitating age-associated neurodegenerative disorder. Currently, no therapy has been shown to unequivocally retard or arrest the progression of the disease. The aim of the present study was to investigate the protective effect of piperine on the 1-methyl-4-phenyl-1,2,3,6‑tetrahydropyridine (MPTP)-induced Parkinson's mouse model. For MPTP treatment, the animals received repeated intraperitoneal injections (i.p.) of MPTP (30 mg/kg) solution for 7 days. Piperine (10 mg/kg) was administered orally for 15 days including 8 days of pretreatment. Motor behavior analysis was conducted with the rotarod test. The Morris water maze (MWM) was used to assess the cognitive learning ability of the mice. A histological examination was subsequently conducted. The results ddemonstrate that piperine treatment attenuated MPTP-induced deficits in motor coordination and cognitive functioning. Piperine also prevented MPTP-induced decreases in the number of tyrosine hydroxylase-positive cells in the substantia nigra. Additionally, piperine reduced the number of activated microglia, expression of cytokine IL-1β, and oxidative stress following MPTP treatment. An anti-apoptotic property of piperine was identified by maintaining the balance of Bcl-2/Bax. In conclusion, the results show that piperine exerts a protective effect on dopaminergic neurons via antioxidant, anti-apoptotic, and anti-inflammatory mechanisms in an MPTP-induced mouse model of PD. Thus, piperine is a potential therapeutic treatment for PD.