Abstract: About 50% septic patients develop sepsis-associated encephalopathy (SAE), which might lead to a worse severe prognosis. Until now, effective treatments are not available for this complication. The major treatment is based on the management of protopathy, combined with the handling of relevant complications or medical practices, such as delirium, pain, mechanical ventilation weaning, and early movement. Recently, many experiments focusing on the therapeutic pharmacy are performed to target neuroinflammation, protection of blood brain barrier, cellular energy metabolism, necrosis, and neural restoration. Notably, traditional Chinese medicine shows therapeutic effects in SAE trials. As rapid advancement in new medical techniques, the clinical treatment for SAE is expected to be improved in the future.