Cadmium (Cd) causes a broad spectrum of toxicological effects to animals. Aquatic animals were more likely to accumulate Cd than terrestrial animals because of the living environment. Clearance of Cd in aquatic animals has become an important part of aquatic food safety. The present study was focused on the oxidative damage induced by Cd in the liver of grass carp Ctenopharyngodon idellus and the protective effect of vitamin E (VE) and metallothionein (MT). Grass carp were divided into four groups: the control group, Cd+phosphate-buffered saline (PBS) group, Cd+VE group, and Cd+MT group. All fish were injected with CdCl2 on the first day and then VE, MT, and PBS were given 4 days after injection, respectively. The liver function and antioxidant capacity of grass carp were evaluated. Cd administration resulted in damage of liver function and morphology in liver, which was expressed as the increased content of AST and ALT, rupture of organelles, and decrease of CAT, SOD, and GSH-Px activity. However, VE and MT treatments protected against Cd-induced damage of liver in grass carp by decreasing AST and ALT content, repairing organelles, and maintained the antioxidant system by elevating CAT, SOD, and GSH-Px activity and regulating related mRNA transcript expression. The results revealed that VE and MT might play an important role in the treatment of heavy metal poisoning through their antioxidative effects.