Abstract: Chronic renal failure (CRF) is associated with multiple complications, a poor prognosis, and limited therapeutic options. Recent studies have shown that the competitive endogenous RNA (ceRNA) network mediated by long non-coding RNAs (lncRNAs) and circular RNAs is widely involved in pathological processes of CRF, such as inflammation activation, oxidative stress, apoptosis, renal fibrosis, extracellular matrix component and structural remodeling, and ferroptosis. It mediates the formation of the pathological loop of “inflammation-injury-fibrosis” during the progression of CRF, thus making it a potential therapeutic target. However, most current studies focus on a single ceRNA axis and lack systematic analysis of the central nodes and dynamic regulatory mechanisms of the network. This article reviews the mechanism of the ceRNA network in CRF and analyzes the intervention effect of traditional Chinese medicine (TCM) on key targets of the ceRNA network, providing a new perspective for interpreting the effects of TCM from the perspective of molecular biology. The “multi-component, multi-target” characteristic of TCM is highly consistent with the complexity of the ceRNA network. TCM can effectively delay the occurrence and development of CRF through multiple pathways, such as anti-inflammation, anti-renal fibrosis, improving cell injury and apoptosis, and reducing extracellular matrix deposition.