Abstract: To investigate the effects of dietary methionine restriction (MR) and leucine restriction (LR) on hepatic fat deposition and oxidative stress in atherosclerotic (AS) mice. Twenty-four male ApoE-KO mice were randomly distributed into 3 groups based on body weight: the AS model group (AS), the methionine-restricted intervention group (AS+MR), and the leucine-restricted intervention group (AS+LR). MR and LR continued the intervention for 8 weeks, and body weights, food intake, and water intake were recorded weekly in mice. After 8 weeks of feeding, the mice were sacrificed. The weight of adipose tissue, liver, heart, and other organs were measured. The changes of aortic plaques and liver tissue morphology and structure were evaluated. Hepatic and plasma lipid levels were examined. The levels of hepatic and plasma redox status indicators were examined. Compared with AS mice, AS + MR mice exhibited significantly reduced body weight, adipose tissue, and liver weight (P＜0.05), significantly increased food intake and water intake, significantly reduced plaque area in the arteries (P＜0.05), reduced fatty infiltration area in liver tissue (P＜0.05), significantly reduced hepatic and plasma levels of TG, TC and LDL-C, and significantly increased hepatic and plasma levels of HDL-C (P＜0.05). Furthermore, AS + MR mice exhibited significantly increased hepatic and plasma levels of T-AOC, T-SOD, T-GSH, GSH/GSSG, significantly decreased hepatic and plasma MDA levels (P＜0.05), where GSH-PX was also significantly increased in liver (P＜0.05). Compared with AS mice, AS +LR mice showed significantly decreased body weight, epididymal fat mass and liver weight (P＜0.05), significantly increased food intake and water intake, significantly reduced plaque area in the arteries (P＜0.05), significantly decreased hepatic TC and plasma TC, TG, and LDL-C levels (P＜0.05), and significantly increased plasma HDL-C levels (P＜0.05). Meanwhile, LR improved the redox status due to markedly decreased hepatic and plasma MDA levels (P＜0.05), and significantly increased hepatic T-AOC, T-SOD, T-GSH and GSH/GSSG (P＜0.05) and plasma T-AOC and T-GSH levels (P＜0.05). Compared with AS+LR mice, AS+MR mice displayed significantly decreased body weight, epididymal fat mass and liver weight (P＜0.05), significantly increased food intake and water intake, significantly decreased hepatic TC and LDL-C levels (P＜0.05), significantly increased hepatic and plasma HDL-C levels (P＜0.05), significantly increased hepatic T-GSH and plasma T-GSH and T-SOD levels (P＜0.05), and significantly decreased hepatic and plasma MDA levels (P＜0.05). These results demonstrate that both MR and LR have the effects of improving hepatic fat deposition and oxidative stress in AS mice, which prevent the development of AS disease. MR has better intervention effects than LR. This study provides a novel approach and theoretical basis for the prevention and improvement of the current high prevalence of AS disease.