The exercise involving hundreds of soldiers, anti-terrorist police, firefighters and government officials took place in the resort of Gori, on the southeast coast, the ministry said.
The plant has four reactors, including the first built in 1978 and four more are under construction.
The drill - inspected by Han Min-Koo, chairman of the Joint Chiefs of Staff - simulation of the infiltration of North Korean agents to bomb a nuclear power plant, a ministry spokesman told the AFP.
"Our nation faces a very dangerous situation in case of emergencies of any kind in nuclear power plants," Han said in a statement, calling for "the perfect disaster preparedness."
The nuclear crisis in neighboring Japan and South Korea has led to perform security checks in their own plants.
South Korea operates 20 nuclear plants that generate about 35 percent of its electricity needs, and plans to build 12 more over the next 14 years.
Its oldest reactor in Gori became accidentally out on Tuesday due to an electrical fault in the midst of growing controversy over the extension of his life.
There was no security risk to the reactor of 587 thousand kilowatts and no radiation leak, state-run Korea Hydro and Nuclear Power, said, adding that he was repairing an electrical component.
The reactor became temporarily in 2007 to end of their operating life of 30 years. However, the operators received government approval last year to be in line for another 10 years after changes to security systems.
Environmentalists have demanded its closure.
The nation is committed to adhere to its program to develop nuclear energy despite the major concern in the world after the Japanese crisis.
"The dependence of South Korea in the energy intensive industries that are virtually impossible to give up nuclear energy," said Knowledge Economy Minister Choi Joong-Kyung a business forum on Wednesday.