Cadmium (Cd) is a type of noxious heavy metal that is distributed widely. It can severely injure the hepatocytes and cause liver dysfunction by inducing oxidative stress and mitochondrial damage. We evaluated the protective effects of α-lipoic acid (α-LA) or chlorogenic acid (CGA) and their combination on counteracting cadmium toxicity in vivo in three-yellow chickens. For three months, CdCl2 (50 mg/L) was administrated through their drinking water, α-LA (400 mg/kg) was added to feed and CGA (45 mg/kg) was employed by gavage. The administration of Cd led to variations in growth performance, biochemical markers (of the liver, kidney and heart), hematological parameters, liver histopathology (which suggested hepatic injury) and ultrastructure of hepatocytes. Some antioxidant enzymes and oxidative stress parameters showed significant differences in the Cd-exposure group when compared with the control group. The groups treated with Cd and administrated α-LA or CGA showed significant amelioration with inhibited mitochondrial pathway-induced apoptosis. Combining both drugs was the most effective in reducing Cd toxicity in the liver. In summary, the results demonstrated that α-LA and CGA may be beneficial in alleviating oxidative stress induced by oxygen free radicals and tissue injury resulting from Cd-triggered hepatotoxicity.