Depression is a prevalent mental disorder characterized by a multifaceted pathogenesis involving theories such as neurotransmitter dysregulation, microglial activation, hypothalamicpituitary-adrenal (HPA) axis dysregulation, inflammasome activation, microbiome alterations, and impaired neuroplasticity. Current first-line antidepressants, including selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), exhibit limitations such as delayed onset, low efficacy rates, and significant interindividual variability. In recent years, driven by advances in molecular biology and immunopsychiatry research, growing evidence has indicated an interplay between immune-inflammatory pathways and depression. The kynurenine pathway, a predominant route for tryptophan metabolism, generates metabolites that play significant roles in neural, immune, and inflammatory regulation, particularly exhibiting complex dual effects in immune modulation. It is essential to construct a comprehensive view of the peripheral-central immune network and delve into the mechanistic role of the tryptophankynurenine metabolic pathway within this network in the pathogenesis of depression, thus further advancing our knowledge of the pathophysiological mechanisms of depression and facilitating drug development.