Facial palsy, often resulting from trauma or iatrogenic treatments, leads to significant esthetic and functional impairment. Surgical interventions, such as masseteric-to-facial nerve transfer combined with static suspension, are frequently recommended to restore facial nerve function and symmetry. This study examines how Botulinum Toxin A (BoNT-A) treatment on the unaffected side affects facial symmetry and brain connectivity in patients with severe oral commissure droop from facial nerve damage. Patients were divided into two groups: one received BoNT-A injections on the unaffected side, and the other did not. Our findings revealed that BoNT-A treatment not only improved facial symmetry but also induced significant modifications in brain functional network connectivity. These modifications extended beyond the sensorimotor network, involving high-level cognitive processes, and exhibited a significant correlation with the degree of facial asymmetry. These results provide valuable insights into the mechanisms underlying the positive effects of BoNT-A intervention on motor recovery and brain plasticity in facial palsy patients. Furthermore, the study emphasizes the importance of a multidisciplinary approach to facial palsy rehabilitation. Understanding these intricate interactions between facial symmetry restoration and brain network adaptations may pave the way for more effective treatments and improved quality of life for individuals dealing with facial palsy.