Shepherd played Stewart in NBC's top-rated "Martha, Inc." in 2003 and has reprised the role for "Martha: Behind Bars" (search) (9 p.m. EDT).
"I looked at it as a completely different project and a completely different character," Shepherd told the New York Post's Michael Starr in May.
"I didn't even refer to the prior movie, and I haven't watched it since it originally came out," she said. "I thought I'd watch [the first movie], but then I realized, no, this is a different movie and a different person.
"It's a great opportunity for me to play such an extraordinary woman who's had such a profound effect on all of us."
"Martha: Behind Bars" will document Stewart's very public downfall, culminating in her prison sentence for lying to federal investigators and her subsequent post-prison renaissance.
"It's a fascinating, ongoing story, one of the great stories of all time, I think," Shepherd said of Stewart's life. "She's a great woman, and I have great admiration for her, now more than ever.
"She's totally being treated unfairly. It was very personal over a very small mistake and she's suffered, she's paid her dues and she came out on top."
Shepherd is most famous for "Moonlighting," the stylistically groundbreaking ABC series (1985-89) on which she starred with Bruce Willis.