The gut microbiome is known to be involved in depression development. Thus, phytochemicals changing gut microbiota may alleviate depression-like behaviors. Coniferyl ferulate (CF) is a long studied natural product and known to alleviate psychiatric disorders. However, its mechanism of action remains unclear. In this experimental study, oral administration of 50 mg kg-1 CF once daily attenuated weight loss and depression-like and anxiety-like behaviors induced by chronic unpredicted mild stress (CUMS) in mice. Four weeks of CF administration significantly ameliorated colonic inflammation, lowered the levels of IL-6, IL-1β, and TNF-α, and restructured the gut microbiome, and microbial metabolism. Intestinal microbiota can impact the development and function of the brain via the microbiota-gut-brain axis. Therefore, oral administration of CF is a promising nutritional strategy to treat CUMS-induced depression via the regulation of microbiota and microbial metabolism.