The activists got into the four-reactor plant at Tricastin near Avignon before dawn, and displayed banners bearing President Francois Hollande's image and the slogan: "Tricastin nuclear accident. President of catastrophe?"
They also projected the slogan "Tricastin nuclear accident" and a forked line representing a fissure in green letters on the wall of a building. The interior ministry said all 29 activists involved in the protest had been detained.
None had been able to gain access to sensitive areas "namely the control rooms," the ministry said.
Greenpeace said the action was aimed at pressuring Hollande to close the 33-year-old plant, which it calls "one of the five most dangerous facilities in France." The organisation points to multiple cracks on the reactor vessel no. 1, and to the plant's location in an area at risk of flooding and tremors, as proof that it is a safety hazard.
The French nuclear safety authority says the fissures pose no safety threat and has cleared the plant to remain in service.
Greenpeace has staged a number of protests inside French nuclear power plants since the Fukushima disaster in Japan in 2011. The campaign, which has embarrassed the French government, aims to demonstrate the vulnerability of the plants to attack.
But France remains wedded to nuclear power, which provides three-quarters of the country's electricity.
Hollande has promised to reduce the share of nuclear in the France's energy provision to 50 per cent by 2025.
So far he has announced plans to close one plant, at Fessenheim, on the border with Germany.
Greenpeace says more plants need to be closed if the president is to meet his target.