The original Japanese version is an interesting case: This is the first Ghibli movie that doesn't use professional voice actors for the main characters, relying entirely on celebrities for them. The only known professional with a named role in the movie is Sumi Shimamoto as Toki, Lady Eboshi's servant.
Cross-Dressing Voices: Moro is voiced by a man in the Japanese version. This comes from Japanese mythology which says that wolves are always male-voiced (and cats always female-voiced), regardless of sex.
Executive Meddling: Thankfully averted, as opposed to earlier efforts to adapt Miyazaki's films into English. Miramax (read: the Weinstein brothers) wanted to cut 20 minutes from the English release, which was explicitly forbidden by the Disney/Ghibli distribution agreement. When Studio Ghibli producer Toshio Suzuki found this out after a very successful screening for the New York Film Critics Circle, he allegedly sent the Miramax executives a katana with a note attached: "No cuts."
Keep Circulating the Tapes: Disney's sale of Miramax was in the way of any possible re-release in America for several years. Miramax's rights lapsed at some point and Disney re-issued the film (officially re-printing the original DVD release from Buena Vista Home Entertainment re-badged in Disney's Ghibli package design) in 2012.
Last Of Its Kind: This is Studio Ghibli's final film to be drawn & colored on plastic cels, and is often thought to be the last cel-animated film in the world chronologically. After Mononoke, Studio Ghibli switched to digital animation because cel animation had become too financially impractical.
The earliest concepts Miyazaki had that involved a Mononoke spirit was actually his re-telling of Beauty and the Beast.
Leonardo DiCaprio was considered to voice Ashitaka in the English dub. Possible Casting Gag since Claire Danes was the voice of San, which would have made this the second time they had been Star-Crossed Lovers.