The Oscar-winning actress, who made her big screen breakthrough in the 1990 romantic comedy, told Moviehole that she won't reprise her role as prostitute Vivian Ward because "nobody wants to see an old hooker".
"It's not that I'm anti romantic-comedy, which, for some reason, is always the favoured interpretation," she said. "’I like being funny, I like being romantic... but it's challenging trying to find a script which is original or interesting."
Several screenplays have been written for a Pretty Woman 2, but Roberts, co-star Richard Gere and director Garry Marshall have declined offers to make a sequel. However, the trio did reunite for the 1999 comedy Runaway Bride.
Roberts can next be seen in Marshall's new movie Valentine's Day, due for release on February 12.