"A car bomb driven by a suicide bomber tried to force its way into the western entrance of the ministry complex," a security official told AFP.
"It was followed by another car whose occupants opened fire at the complex of buildings," he said.
"There are dead and wounded," another security source said after a strong explosion was heard across the capital, without giving any immediate figures.
Plumes of smoke billowed across the complex, situated on the edge of the Baba al-Yaman neighbourhood, and gunfire was heard.
The attacks in the capital and in the country's south have been blamed on Al-Qaeda in the Arabian Peninsula (AQAP), which Washington regards as the jihadist network's most dangerous branch.
Yemen has been going through a difficult political transition since veteran president Ali Abdullah Saleh was ousted in February 2012 after a year of deadly protests against his 33-year rule.