The Angus South MSP told Nicola Sturgeon that while it had been an “absolute privilege” to hold the post, he was no longer able to give this “hugely important ministerial role everything it rightly requires”.
Mr Dey became the transport minister following a post election reshuffle in May last year.
Prior to that he had served as a the parliamentary business and veterans minister since June 2018.
In a letter sent to the First Minister, Mr Dey said: "I have always prided myself on being able to give 100 per cent to any task I am charged with.
"Regrettably, despite my continuing passion, I find myself unable to now give this hugely important ministerial role everything it rightly requires and deserves.
"It is therefore with regret that I am writing to resign from office as minister for transport in the Scottish Government.
"This is entirely for personal reasons related to my health and well-being.”
Mr Dey added: “In the immediate future, I intend to focus on improving my health and well-being and on giving more attention to my family, while also continuing as MSP for Angus South to serve the needs and interests of the people in my constituency.”
Ms Sturgeon said Mr Dey had been a “highly effective minister” who had “many achievements to his name”.
The First Minister said: “As minister for parliamentary business, he built trust and confidence across the political spectrum to navigate a period of minority Government, and ensure that Government remained accountable to Parliament throughout the period of lockdown earlier in the pandemic.
“As transport minister, Graeme played a huge part in ensuring the success of COP26.
“He has also delivered concessionary bus travel for under-22s, set out plans to reduce car travel to meet climate targets, and prepared the ground for the return of Scotland’s railway to public ownership.”
She continued: “Circumstances permitting, the door will always be open should Graeme wish a return to Government in future.”