Objectives: This study aimed to examine the feasibility of nasal powder formulations for the delivery of levodopa (L-dopa) into the brain using highly water-soluble levodopa methyl ester hydrochloride (LDME). Methods: For designing nasal LDME powders, pH-rate stabilities of LDME in buffer solutions and their enzymatic degradations in rabbit nasal mucosal and serosal extracts were investigated. In vitro permeation studies were carried out with four LDME nasal powders. Results: LDME was degraded fast in weakly acidic and neutral solutions, but relatively stable in acidic solutions. In nasal extracts, LDME (50 and 200 μg/mL) was rapidly hydrolyzed, forming L-dopa, and there were no significant differences in first-order degradation rates between mucosal and serosal extracts. From the in vitro permeation studies, LDME powder formulations resulted in faster appearance rates (1.07 ± 0.39 mg/cm2/hr) of L-dopa than solution formulations (0.35 ± 0.08 mg/cm2/hr). Conclusions: These results suggested that LDME nasal powder formulations could be useful delivery systems of L-dopa.