In the present review, we describe here experimental comparative and beneficial effects of botulinum neurotoxin A (ANTX) between subtypes A1 and A2 in the pathology of movement disorders, particularly rat Parkinson’s disease model. We and other laboratories have shown the beneficial effects, and this novel strategy for intractable brain disorders might confer potent and safety therapy in bedside. First, we show the characteristics of ANTXs in the genetic aspects of these subtypes, and our intriguing findings of immunological profiles in the subtypes between A1NTX and A2NTX. Then, we state the distinct diffusion in the body between A1NTX and A2NTX. Importantly, we describe that the intra-brain treatment of small animals with A2NTX subtype results in improvements of pathologies more effectively and provides greater safety than those of A1NTX in a rat 6-OHDA Parkinson’s disease (PD) model. Finally, we represent that the different efficacies between ANTXs are likely due to each localization in the brain; A2NTX is strictly limited in the injected regions, while A1NTX diffused other brain regions. Thus, therapeutic avenue using A2NTX in incurable PD including other movement disorders could be a druggable target in the future.