Depression is a common mental disorder, the pathogenesis of which involves such factors as the imbalance of the monoamine system, neuroinflammation, and oxidative stress. Depression has been found to be associated with dysfunction in the blood-brain barrier (BBB). In recent years, cannabidiol (CBD) has attracted extensive attention due to its remarkable antidepressant activity and neuroprotective properties. Of particular interest is the possibility that CBD may combat depression by repairing BBB damage and thereby improving the homeostasis of the central nervous system. Based on recent research findings, this article explores the antidepressant mechanisms of CBD, the BBB damage in depression, and the protective effects of CBD on the BBB. It is expected to provide references for subsequent studies on the mechanisms of BBB damage in depression and the discovery of new antidepressant targets.