The actor starred as Mr Big in the long-running comedy series, with his character marrying Sarah Jessica Parker's Carrie Bradshaw in 2008's Sex and the City: The Movie.
"Sex and the City - it's the cancer," Noth told the Irish Times while promoting his new miniseries Titanic: Blood and Steel.
"Global media, you can't get away from it. I'm laughing. There is not much for me to say about it anymore. It is hard to try and rediscover new ways for yourself to be excited about it."
Sex and the City 2, which took Parker, Kim Cattrall, Kristin Davis and Cynthia Nixon to Abu Dhabi, grossed more than $280 million at the worldwide box office in 2010 but was met by a barrage of negative critical reviews.
The comedy sequel sits at just 15% on reviews aggregator Rotten Tomatoes.
In September it was reported that a Sex and the City prequel TV series was being developed by Gossip Girl producers Josh Schwartz and Stephanie Savage.
Noth's Titanic: Blood and Steel will air in the UK next year.
Watch the Sex and the City 2 trailer below: