The role of the gut microbiota in the pathophysiology of depression has been explored in numerous studies, which have confirmed that the baseline gut microbial profiles of patients with depression differ from those of healthy individuals. The gut microbiome affects metabolic activity in the immune and central nervous systems and regulates intestinal ecology through the neuroendocrine system. Additionally, baseline changes in the gut microbiota differed among patients with depression who demonstrated varying treatment response. Currently, probiotics are an emerging treatment for depression; however, the efficacy of modulating the gut microbiota in the treatment of depression remains uncertain. Additionally, the mechanisms by which changes in the gut microbiota affect treatment response in patients with depression remain unclear. In this review, we aimed to summarize the differences in the baseline gut microbiota between the remission and non-remission groups after antidepressant therapy. Additionally, we summarized the possible mechanisms that may contribute to antidepressant resistance through the effects of the gut microbiome on the immune and nervous systems, various enzymes, bioaccumulation, and blood-brain barrier, and provide a basis for treating depression by targeting the gut microbiota.