The incident comes amid an escalation of missile strikes by Yemen's Iran-aligned Houthis on the kingdom.
The incident caused a fire in a vehicle outside the facility's perimeter but did not affect operations at the field, the ministry said, citing an official source.
"The attempted attack resulted in the deaths of two residents, one Filipino and one Nepali, and injuries to two residents, one Pakistani and one Indian due to falling debris following the interception," the ministry said.
Saudi Arabia has responded to Houthi attacks with a wave of strikes on missile launcher sites, vowing to protect the kingdom, and says it has intercepted many ballistic missiles fired by the group.
Last month, debris from an intercepted Houthi drone killed a Yemeni resident of Saudi Arabia. It was the first civilian casualty since the Houthis increased their attacks against the kingdom, targeting Saudi shipping and oil facilities.
Earlier this month, a limited fire broke out in an administrative building at Aramco, one of the world's largest oil facilities, targeted in an attack in Saudi Arabia's Eastern Province, the energy ministry said at the time.
The attacks come as renewed fighting between the Houthis and the Saudi-backed government forces has broken a four-year truce. The fighting in Yemen marked a fresh escalation in the widening Middle East crisis.
Riyadh's King Khalid International Airport, which was struck multiple times by the Houthis this month and shut down on October 10, was open for domestic flights Wednesday. Saudia and FlyNas were operating flights, according to FlightAware data. Major carriers, including Lufthansa and Air France, have cancelled service through mid-November.
The Houthis have acknowledged attacking the airport, claiming without evidence that Saudi Arabia provided military equipment to government forces through the facility.
with AP and DPA
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