The ministry said on Tuesday that the flotilla has left the Baltic port of Baltiysk and is sailing for the Mediterranean.
It said the flotilla includes the frigate Yaroslavl Mudry, the landing ships Kaliningrad and Alexander Shabalin as well as two other vessels.
The ministry said that the Russian naval ships would carry out training drill after replacing another fleet in the Mediterranean.
Citing military sources, the Interfax news agency reported last week that the flotilla could be used to evacuate the Russians living in Syria in case the situation in the country worsens.
Russia, a key ally of Syria, has a small naval maintenance facility at the Syrian port of Tartus in the Mediterranean Sea.