Highways England are planning to carry out further improvement works to the A628 Woodhead Pass, between Tintwistle and Crowden.
The work will start on Monday 1 February and is set to last around 10 weeks.
It includes stabilisation work between Crowden and Tintwistle and replacing the safety barrier at Salter’s Brook.
Most of the work will use 24/7 temporary traffic lights. However, there will be a full weekend closure and five overnight closures to complete excavation and piling work.
The weekend closure is planned from 8pm on Friday 5 March until 6am on Monday 8 March.
Highways England say it's part of its £5 million investment for the A628, providing "safer and smoother roads and more reliable journeys for people using this strategic route".
The government company has previously said it hopes to complete the maintenance and improvement work on the major road by the end of March.
Repairs to five walls on the route are now completed. Work to prevent flooding on the A628 includes 933 metres of new drainage, 1,200 metres of new road markings, 140 new reflective road studs, and 130 metres of new kerbing.
Along the embankment close to Longside, works have removed the damaged gabion baskets, replacing the damaged soil nails and steel wire mesh, and reconstructing the pile foundations which were damaged after an accident.
Nine miles of the A628 has been resurfaced, which will provide drivers with smoother and safer journeys. This has also included some high friction surfacing, which will further improve safety for drivers.
High Peak MP Robert Largan said: "I have asked Highways England to keep disruption to a minimum. But please be aware this may cause more traffic through Glossop and on the A57.
"This is part of a £5million investment into the A628, which is welcome. However, the most pressing need is to get on and build the Mottram Bypass and find a traffic solution for Tintwistle. We're making significant progress, with the recent milestone of Balfour Beatty being appointed to build the bypass. But I'll keep fighting until we get it built!"