Parkinson?s disease (PD) higher incidence has been observed in postmenopausal women compared to premenopausal women, suggesting estrogen neuroprotective effect. L-DOPA (LD) chronic treatment causes dyskinesia; evidences indicate that LD increases the preexisting oxidative stress condition. This study determines melatonin ability, alone or in combination with LD (LD/Mel) to protect dopaminergic loss induced by 6-OHDA in a rat PD model in ovariectomized (OVX) and intact (with ovaries (W/OV)) rats on motor behavior and cytological alterations, comparing with LD-only treated rats. LD/Mel-treated rats showed dyskinesia decrease (score 5–7.5) and had the best performance in the staircase test (five pellets) throughout all studies. The beam walking time was 20–35 s, showing good coordination (as control group (20–38 s)), dopaminergic cells increase of 22.8% (W/OV rats) and 27.2% (OVX rats) in the contralateral side as well as 100% conservation in the contralateral dendritic spines. Our results suggest that LD/Mel co-administration and estrogen presence result in an efficient treatment to reduce dyskinesia through the conservation of some dopaminergic cells, which imply a well-preserved neuropil of a less denervated striatum. We assume that these results are because of a synergistic effect between LD, melatonin and estrogens.