The Portuguese forward, 27, joined United for £12 million from Sporting Lisbon in 2003 and left for Real Madrid for a world record fee of £80 million in July 2009.
Coincidentally, he will be playing again in Manchester on Wednesday - but for Real at Manchester City in the Champions League.
"I'd like to think the door would always be open for him to come back, but I don't think it will happen," said Ferguson.
"You're talking about incredible amounts of money now. What would you think his value would be?
"He's definitely unbuyable. Who could afford to buy him? There's talk of the Russians perhaps. But do you think he would go to Russia?
"He complained about the weather here, let alone the middle of winter in Russia."
Ronaldo won three Premier League titles at United as well as the Champions League in 2008 and has since gone on to contend for the title of the world's best player with Barcelona rival Lionel Messi since moving to Spain three years ago.
"He was definitely good value for Real Madrid, but he always wanted to play for them. It was his boyhood dream. I am not saying he will stay there forever, you never know," Ferguson added.
"How do you know we've not got a buy-back clause for him?"
