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Depression imposes significant social, economic, and health burdens worldwide. Although phlorotannin-rich extract from Ecklonia cava (PS) and its active compound dieckol (DK) exhibit various biological activities, their antidepressant- and anxiolytic-like effects and underlying mechanisms remain unclear. This study investigated the antidepressant- and anxiolytic-like potential of PS and DK in a corticosterone (CORT)-induced mouse model of depression and anxiety, focusing on glucocorticoid receptor (GR) signaling. CORT-treated mice were orally administered PS or DK, and behavioral tests were performed to assess depressive- and anxiety-like behaviors. PS composition was analyzed using LC-MS/MS. Molecular docking predicted the binding of PS components to GR. GR nuclear translocation, target gene expression, and downstream signaling were examined using behavioral, molecular, and computational approaches. PS alleviated CORT-induced depressive- and anxiety-like behaviors, accompanied by reduced GR nuclear translocation, suppression of Mkp-1, and restoration of ERK-CREB-BDNF signaling. Molecular docking analysis predicted strong binding of DK to the GR ligand-binding domain. Consistently, DK reduced GR nuclear translocation and GRE binding, downregulated GR target genes (Mkp-1, Sgk-1, Fkbp5, and Bdnf), and restored ERK-CREB-BDNF signaling. In vivo, DK also improved CORT-induced behavioral deficits and normalized HPA axis activity and neurotransmitter levels. Collectively, our results suggest that DK, a major bioactive phlorotannin from E. cava, exerts antidepressant- and anxiolytic-like effects in association with modulation antagonism of GR signaling, highlighting its therapeutic potential as a natural GR-modulating agent for stress-related mood disorders.