Abnormal activation of programmed cell death (PCD) plays a key regulatory role in the progression of kidney injury and fibrosis, and different modes of PCD can participate in the occurrence and development of chronic kidney disease (CKD) through diverse pathological mechanisms. Autophagy has a "double-edged sword" effect. Its moderate activation can maintain cellular homeostasis and retard renal fibrosis by clearing damaged organelles and misfolded proteins. However, its excessive activation or impaired function leads to the accumulation of harmful substances and mitochondrial dysfunction, thereby accelerating the progression of kidney diseases. Necroptosis mediates inflammatory responses and promotes renal fibrosis via the receptor-interacting protein kinases 1/3 (RIPK1/RIPK3)-mixed lineage kinase domain-like protein (MLKL) signaling pathway. Pyroptosis relies on the activation of the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome, which promotes the release of pro-inflammatory factors and aggravates renal injury. Ferroptosis participates in the pathological process of CKD through lipid peroxidation and iron-dependent mechanisms. Targeted therapeutic strategies for the aforementioned PCD have exhibited potential renal-protective effects in various preclinical models, including diabetic kidney disease, unilateral ureteral obstruction, 5/6 nephrectomy, and acute kidney injury. This paper reviews the roles, mechanisms and interactions of the four PCD modalities in CKD. In the future, machine learning can be leveraged to optimize multi-target combination therapies (e.g., quercetin derivatives synergistically regulating ferroptosis and necroptosis), realize patients stratification and therapeutic effect prediction, and provide a new paradigm for precise intervention of CKD.