Roadworks are scheduled to take place on the A75 Layby to Kirtle Water east and westbound.
Over £360,000 of resurfacing works will be undertaken by Scotland TranServ on behalf of Transport Scotland.
The road will be closed from 7pm on 5 June until 6am on 8 June.
Gordon Wilson, Contract Director at Scotland TranServ said: "This essential maintenance scheme is vital to ensuring we prolong the lifespan of the road surface benefiting road users using the A75.
"We are doing everything we can do minimise disruption by carrying these works out over the weekend however we would advise motorists to plan ahead and leave plenty of time for their journeys."
(LM)
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