The two "terrorists" were killed in the mountainous area of Orbata in Gafsa, the ministry said in a statement, adding that the operation was ongoing.
Tunisia, the cradle of the Arab Spring uprisings, has been hit by repeated militant attacks in recent years.
'Terrorist attack' kills six Tunisia security forces
In July, the Islamic State (IS) group - which has carried out multiple bloody attacks in Tunisia - called for new attacks, in a video purportedly filmed in the country.
The release of the video came three weeks after a double suicide attack against police in Tunis claimed by IS that killed two - a police officer and a civilian.
On October 29, 2018 an unemployed graduate blew herself up near police cars on Habib Bourguiba avenue, killing herself and wounding 26 people, mostly police officers, according to the interior ministry.
Tunisia pays tribute to security forces killed in militant attack
In March 2015, militant gunmen killed 21 tourists and a policeman at the National Bardo Museum in Tunis.
In June that year, 30 Britons were among 38 foreign holidaymakers killed in a gun and grenade attack on a beach resort near the Tunisian city of Sousse.
And in November 2015, a suicide bombing against a bus carrying presidential guards killed 12, in an attack claimed by IS.
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