The mudslide occurred on Sunday night in Jalalabad province, 300 km south of the capital, Bishkek.
A total of 209 houses were hit in villages in Jalalabad's Suzak district, 75 in Bazarkorgon district and 42 in Nooken district, with many more households affected by the flooding, the MOE said.
An MOE team is carrying out rescue operations, including evacuating people from affected areas. However, local people are unwilling to abandon their homes and cattle, MOE spokesman Alisher Tashmatov told IRIN from Bishkek.
"People have been evacuated in certain places, but the thing is there are a lot of cattle there. People won't leave them," Tashmatov said. There were no preliminary reports of casualties.
This is the second time southern Kyrgyzstan has been hit by floods and mudflows over the past few days. Mop-up operations are still under way in the area after heavy downpours caused floods and mudslides last week in Jalalabad and neighbouring Osh province.
In the Aksy district of Jalalabad province, 500 schoolchildren have been drafted in to assist the clear-up operation after mudflows hit villages on 17 April. Just less than 200 homes in the district were flooded, the MOE said on Tuesday.
The Kyrgyz Red Crescent Society has sent humanitarian aid to the district, including bedding and cooking equipment, and the MOE has provided clothing, flour and tea.
Kyrgyzstan is vulnerable to more than 20 different types of natural disasters, according to the UN Economic and Social Council.
Last year Emergencies Minister Janysh Rustenbekov said about 3.5 million people out of Kyrgyzstan's 5.2 million population were living in disaster-prone areas.
Southern Kyrgyzstan is at particular risk. A UN Development Programme (UNDP) survey published last year showed that the main problems in Osh province are landslides, while in Jalalabad the biggest risk is floods.
This winter the country was hit by four earthquakes in little over a month, beginning in December when tremors destroyed 1,332 homes and left about 6,700 people homeless in the central Kochkor district.
In January, two earthquakes damaged about 1,300 houses in south-western Batken region, and a smaller quake hit Jalalabad province in February. Major reconstruction work on buildings has not yet started due to weather conditions.