Metal ion-dependent regulated cell death pathways, centered on ferroptosis and cuproptosis, play key roles in fibrotic diseases. Disruptions in the cellular uptake, storage, and efflux of iron and copper ions lead to redox imbalance, which subsequently activates the canonical and non-canonical transforming growth factor-β/Smad pathways, drives epithelial-mesenchymal transition (EMT) and fibroblast-myofibroblast transition (FMT), and promotes the release of damage-associated molecular patterns to amplify the inflammation-fibrosis loop, thereby promoting organ fibrosis. The mitochondrial tricarboxylic acid cycle serves as a common convergence point of ferroptosis and cuproptosis. Targeted intervention strategies derived from related pathways, including metal ion chelators, traditional Chinese medicine derivatives, small-molecule targeted drugs, and nanomaterials, show favorable anti-fibrotic potential by restoring metal ion homeostasis, blocking EMT/FMT and inhibiting oxidative stress.