Abstract: Objective: To investigate the protective effects of goat milk casein-derived bioactive peptides on the liver and kidneys of lead-exposed mice. Methods: Goat milk casein-derived bioactive peptides were prepared via enzymatic hydrolysis. The enzymatic hydrolysis process was optimized using single-factor experiments combined with response surface methodology, with lead ion chelation rate as the evaluation index. Ultraviolet (UV) scanning and Fourier-transform infrared spectroscopy (FTIR) were employed to analyze the chelation characteristics between lead and the bioactive peptides. A lead-exposed animal model was established using four-week-old male ICR mice. The protective effects of the bioactive peptides on the liver and kidneys were evaluated by observing hematoxylin-eosin (HE) staining of liver and kidney sections, oxidative stress markers, and inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Results: The optimal enzymatic hydrolysis conditions were determined as follows: Enzyme dosage 3000 U/g, time 2.0 h, substrate concentration 43.97 g/L, temperature 47.60 ^oC, and pH 7.48, achieving a lead chelation rate of 49.60%±0.50%. UV scanning revealed that the binding of lead to the bioactive peptides increased the absorption peak at 237 nm. FTIR analysis indicated that lead reacted with free amino and carboxyl groups in the peptides. The bioactive peptides significantly reduce the liver index in lead-exposed mice (P<0.05), demonstrating protective effects on normal development. They also markedly enhanced superoxide dismutase (SOD) activity (P<0.01), reduced glutathione (GSH) (P<0.01) and malondialdehyde (MDA) levels (P< 0.01), and improved overall antioxidant capacity. Additionally, the peptides significantly decreased IL-6 and TNF-α levels in the liver and kidneys (P<0.01), indicating reduced inflammation. Conclusion: Goat milk casein-derived bioactive peptides exhibit protective effects on the liver and kidneys of lead-exposed mice. This study provides evidence for their potential as natural lead-chelating agents and offers technical support for developing novel lead-eliminating products.