<p>Goal-directed regulation of locomotor behavior represents an important physiological process essential for the survival of humans and other animals. The striatum constitutes a critical component of the basal ganglia and is primarily responsible for processing external inputs. In rodents, the dorsal striatum is primarily divided into two subregions: the dorsolateral striatum (DLS) and the dorsomedial striatum (DMS), both of which are hypothesized to play distinct roles in regulating goal-directed versus habitual behaviors. Recent studies have demonstrated that different subtypes of medium spiny neurons (MSNs) within the dorsal striatum distinctly modulate goal-directed and habitual movements in response to dopamine (DA) and glutamate. Differentiating the DMS from the DLS reveals distinct roles of these subregions in motor control and behavioral decision-making. In the dorsal striatum, D1-MSNs are primarily involved in goal-directed behaviors, while D2-MSNs are more associated with behavior habituation. Early activation of D1-MSNs in the DMS during training enhances behavioral flexibility, concurrent with the inhibition of D2-MSNs in the DLS. However, as training progresses, gradual activation of D2-MSNs in the DLS fosters more stereotyped and habitual movement patterns. Additionally, MSNs critically modulate pathophysiological processes in neurodegenerative diseases. In these diseases, differential activation of the two classes of MSNs—due to specific alterations in the morphological and functional plasticity of MSNs, particularly under conditions of dopaminergic down-regulation—can lead to the development of dyskinesia. Therefore, this paper aims to summarize the effects of goal-directed and habitual motor control on the modulation of motor behavior and explore the neurobiological mechanisms of this system in the development of motor dysfunction related to PD and other related disorders, ultimately offering new perspectives for the treatment and prevention of these diseases.</p>