Casting brought in producer/performer Anthony Begonia to improv audition an unscripted Hawaiian bartender line which didn't make it in the film right before the "Flaming Tornado" is unleashed.
The dragon head katana on Mr. Thompson's desk is the same type made popular by the character Duncan McLeod from the TV show "Highlander" (1992).
In one scene, Dupree is running through a parking lot looking for Carl. In said parking lot, you can see the yellow van from the movie Little Miss Sunshine (2006), which was in production around the same time.
The interior shots of Molly and Carl's house are filmed on the set of what used to be Hope and Michael Steadman's house on the television series "thirtysomething" (1987).
Carl and Molly's house, although it is blue, is the same house used at the end of 13 Going on 30 (2004), where it is pink.
The bumper sticker on Mandy the librarian's car reads "Do the Dewey". Dewey is the decimal system for cataloging library books.
In both _There's Something About Mary (1998)_ and _You, Me and Dupree (2006)_, the character played by Matt Dillon is referred to as "a big mook."
In one of Matt Dillon's first major roles, he plays the bully Mooney in My Bodyguard (1980). When he tells his teacher that he would like to be called "Big M", the lead character, played by Chris Makepeace, incurs his enmity by asking aloud, "Is that B.M. for short?" And then Owen Wilson's favorite gift for having been Matt Dillon's Best Man is the "BM" medallion.
The cover for Dupree's book, "Seven Different Kinds of Smoke," exactly mimics the cover for Lance Armstrong's book, "It's Not About the Bike," which is mentioned a couple times in the movie. Dupree reads Lance's book, and at the end, Lance reads Dupree's book.
Cameo: [Lance Armstrong] who is Dupree's inspiration, makes three cameos in the movie. First, he is seen in the biking video that Dupree exercises to (despite appearances, this is not stock footage, but filmed specifically for this movie). Second, he appears in the dream sequence, where Carl imagines Dupree and Molly on Bob's boat (Armstrong is wearing Dupree's "Say Hello to my little friend" gnome shirt). Finally, in a brief after-the-credits scene, he is shown reading Dupree's book, in exactly the same way that Dupree was seen earlier reading Armstrong's book.
The three main stars of the film, Owen Wilson, Kate Hudson and Matt Dillon all have the same amount of letters in their first names (4) and last names (6).