L-DOPA is the gold-standard therapy for Parkinson’s disease, providing a transient restoration of dopamine (DA) levels. However, chronic administration leads to the development of abnormal involuntary movements, known as L-DOPA-induced dyskinesias (LID), thereby limiting therapeutic efficacy and compromising patients’ quality of life. LID are associated with the interaction between synaptic plasticity induced by dopaminergic denervation and the abnormal pulsatile stimulation of DA receptors. Structural changes in the density of dendritic spines of striatal medium spiny neurons have also been reported, suggesting an anatomical substrate for this phenomenon. The endocannabinoid system has emerged as a promising therapeutic alternative. In particular, cannabidiol, the main non-psychotropic component of Cannabis sativa (CS), exhibits neuroprotective, anti-inflammatory, and dopaminergic neurotransmission-modulating properties. To explore its therapeutic potential on LID, we conducted a pilot study in hemiparkinsonian mice, which received daily CS extract (60 or 120 mg/kg) together with dyskinesiogenic doses of L-DOPA for 14 days. Preliminary results indicate that only the lower dose tends to reduce LID severity. Ongoing studies will evaluate whether CS administration attenuates these dyskinesias and whether its effects are associated with synaptic microarchitectural plasticity in the striatum.