Parkinson‘s disease (PD) arising from the impairment of dopaminergic neurons in the substantia nigra of the midbrain is characterized by accumulation of alpha-synuclein (α-syn). Depression is a precursor of PD and is associated with increased risk of developing PD. Previous research has demonstrated that the administration of calcitonin gene-related peptide (CGRP) to the brain exerts antidepressant effects. Therefore, we hypothesized that there exists a connection between CGRP and PD. In this study, we investigated whether CGRP deficiency or CGRP antibody treatment (galcanezumab) can lead to PD-like symptoms in C57BL6J mice. Motor function was assessed using the rotarod test, pole test, adhesive test, and catalepsy test. Depression-like behavior was assessed using the forced swim test or tail suspension test. Tyrosine hydroxylase (TH) and α-syn expression levels were determined via Western blotting. CGRP-deficient mice showed a significant decrease in motor function and TH levels. An increase in α-syn expression was observed in the substantia nigra and striatum of CGRP-deficient mice. Compared with the control, administration of galcanezumab (once weekly for 4 weeks) resulted in increased depression-like behavior and impaired motor learning. Although dopamine levels in neurons remained unchanged, a notable increase in α-syn expression was observed in the substantia nigra and striatum. These findings suggest that CGRP deficiency can induce PD-like symptoms. Long-term administration of CGRP antibodies may contribute to early-stage PD-like symptoms.