Abstract: To provide the first systematic synthesis of the multifaceted roles of the peroxiredoxin(PRDX) family in kidney diseases, offering novel perspectives for research in this field. Since their discovery in 1987, PRDXs have garnered significant attention due to their unique antioxidant mechanisms and structural characteristics. Family members rely on conserved cysteine residues to reduce peroxides and are classified into 3 subtypes based on structural features: 2-Cys, atypical 2-Cys, and 1-Cys. PRDXs play a central role in regulating oxidative stress, and their functions are closely linked to the onset and progression of various kidney diseases. Studies indicate that serum PRDX levels can serve as oxidative stress biomarkers for assessing the risk of chronic kidney disease and acute kidney injury. Concurrently, different PRDX subtypes exhibit specific functions in various forms of glomerulonephritis. Furthermore, the dynamic changes in the expression abundance and functional activity of PRDX1−PRDX6 in tissues profoundly influence the course of kidney diseases. This review innovatively elucidates the dual roles of PRDXs in kidney pathologies-acting both as a “protective shield” and a “pathogenic factor” along with their intricate regulatory networks. It also explores their significant potential as diagnostic biomarkers and therapeutic targets, alongside the translational challenges they present.