Postpartum depression (PPD) affects approximately 10–15% of women after childbirth and affects the well-being of both mothers and infants. The gut microbiome modulates maternal mood and behavior through the microbiota-gut-brain axis, which involves two-way communication with genetic and epigenetic changes. Changes in gut microbiota are associated with immune dysregulation, inflammation, and neurotransmitter imbalances, which contribute to the pathophysiology of PPD. Genome-wide association studies (GWAS) have revealed genetic risk loci and epigenetic mechanisms such as DNA methylation or histone modifications affecting gene expression. The gut microbiome affects epigenetic changes, including choline metabolism, the dysregulation of which increases the risk of PPD. The article suggests therapeutic options such as probiotics, prebiotics and targeted epigenetic therapies to restore the microbiome and epigenetic balance.