Background <p>Prosopometamorphopsia (PM) is a high-level visual-perceptual disorder characterized by facial distortion. Unilateral PM caused by splenium lesions in the corpus callosum (CC) is rare.</p> Objective <p>To investigate the role of CC splenium lesions in unilateral PM and explore their implications for facial information processing and rehabilitation.</p> Methods <p>We reported four cases of PM due to splenium lesions in the CC and conducted a retrospective analysis of 17 previously reported cases. A comprehensive evaluation framework was developed to assess primary, intermediate, and advanced visual processing in PM patients. Additionally, individualized rehabilitation strategies incorporating avoidance and compensatory methods were implemented.</p> Results <p>CC splenium lesions were identified as the most common cause of unilateral PM, with a tendency toward bottom-up processing. Disconnection syndromes associated with CC splenium lesions were also observed. Patients showed a relatively favorable recovery rate, suggesting dynamic compensatory mechanisms in bilateral facial processing, with stronger compensatory functions in the right hemisphere.</p> Conclusion <p>The splenium of the corpus callosum plays a crucial role in bilateral facial information processing, exerting a lateralized influence on the right hemisphere. Further studies are needed to confirm these findings and elucidate the underlying pathophysiological mechanisms.</p>