Effects of n-acetyl cysteine (NAC), s-ethyl cysteine (SEC), s-propyl cysteine (SPC) and cysteine on enzymes participating in biosynthesis of TAG and cholesterol, and antioxidant protection in liver from mice consuming a high-saturated fat diet was examined. The high-fat diet provided 70 % fat energy, in which saturated fat was 55 % of total fat. NAC, SEC, SPC or cysteine, each agent at 1 g/l, was directly added into the drinking water as a supplement for 4 weeks. Results showed high saturated fat significantly increased hepatic TAG and total cholesterol contents (P < 0·05) via enhancing the activity and mRNA expression of malic enzyme, fatty acid synthase and 3-hydroxy-3-methylglutaryl coenzyme A reductase (P < 0·05). The intake of NAC, SEC or SPC significantly decreased TAG and total cholesterol levels (P < 0·05) via lowering the activity and mRNA expression of these three lipogenic-related enzymes (P < 0·05). NAC, SEC or SPC treatment also significantly suppressed high saturated fat-induced hepatic mRNA expression of sterol regulatory element-binding protein (SREBP)-1c and SREBP-2 (P < 0·05). High saturated fat decreased hepatic content of glutathione, and the activity of catalase and glutathione peroxidase (P < 0·05). The intake of NAC, SEC or SPC significantly increased hepatic glutathione content (P < 0·05), restored the activity and mRNA expression of glutathione peroxidase, and alleviated the high saturated fat-induced oxidative stress (P < 0·05). These results support that NAC, SEC and SPC are potent agents for affecting hepatic biosynthesis of TAG and cholesterol, and protecting liver against high saturated fat-associated oxidative damage.