Background: Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the selective loss of dopaminergic neurons in the substantia nigra. Oxidative stress, neuroinflammation, and α-synuclein aggregation are central pathological features of PD. Zanthoxylum piperitum DC, commonly known as Korean pepper or chopi, is a traditional dietary spice in Eastern Asia and has been reported to possess antioxidant and anti-inflammatory properties. This study investigated the neuroprotective and motor function–enhancing effects of distilled extract of Z. piperitum (deZP) in 1-Methyl-4-phenylpyridinium (MPP⁺)-treated Caenorhabditis elegans and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse models of PD. Methods: In the C. elegans model, dopaminergic neurotoxicity was induced by MPP⁺, and deZP was tested at 0.25, 0.5, and 1% (v/v) to evaluate neuronal preservation through GFP-labeled dopaminergic neurons and α-synuclein expression. Concurrently, in the MPTP-induced mouse model, deZP was administered intranasally at a fixed dose of 20 μL/mouse, equivalent to 5 mg/mouse. Motor function was assessed using the rota-rod test, pole test, and grip strength test, while dopaminergic neuronal survival was evaluated by tyrosine hydroxylase (TH) immunostaining. Results: In MPP⁺-treated C. elegans, deZP significantly restored green fluorescent protein (GFP) fluorescence in dopaminergic neurons and reduced α-synuclein expression, with the most pronounced effects observed at 1% (v/v). In the MPTP-induced mouse model, deZP at this fixed intranasal dose significantly improved motor performance and preserved TH-positive neurons in the substantia nigra. Conclusions: These findings suggest that deZP may represent a promising preclinical candidate for further investigation in PD-related neurodegeneration.