Treatment with WYJYD improves the immobility time in FST, the levels of serum indicators (5-HT, BDNF, and NE), the expressions of hippocampal tissue indicators (FGF2, FOXG1, and p-AKT/AKT), the intestinal microbiota, α-diversity indices, and genera abundance in the rat model of depression. This evidence concerns the gene FGF2 and major depressive disorder.