MacDowell, star of Four Weddings and a Funeral and Groundhog Day, will take to the catwalk with her two daughters at the star-studded New York event at the end of this month.
Billionaire tycoon Donald Trump, who like MacDowell has Scottish roots, has also agreed to play a part in the show.
Organisers hope to secure last-minute appearances from tennis stars Andy and Jamie Murray, along with Scots actor Gerard Butler.
Dressed to Kilt, organised from New York by businessman Geoffrey Scott-Carroll, is one of the centrepiece events of the Tartan Week celebrations, which have been extended to cities across North America and Canada.
The event, which is being held for the seventh time, was shelved last year due to funding problems and Mr Scott-Carroll suffering an illness.
But it is being revived this year with the help of the Scottish Government and VisitScotland, who hope it will provide a huge boost for efforts to promote the Year of Homecoming in the US.
The cheapest ticket for the event costs $99 with a VIP table costing $10,000.
MacDowell, a self-confessed fan of Tunnock's caramel wafers, is just one of a number of American film and TV stars to agree to take part.
They include actor Brendan Fraser, star of the Mummy films, Chris Meloni and Tamara Tunie, from the hit TV show Law and Order, and Ed Westwick, star of Gossip Girl.
Other US celebrities persuaded to strut their stuff on the catwalk are supermodel Maggie Rizer, country singer Kellie Pickler, who shot to fame on American Idol, and New York Giants footballer Lawrence Tynes, who was born in Greenock.
Scottish actress Jensen will be appearing along with fellow Ugly Betty stars Michael Urie and Mark Indelicato.
Other home-grown celebrities due to appear are actor Jason Flemyng, star of The Curious Case of Benjamin Button, supermodel Lauren Tempany, singer Sandi Thom and the current Miss Scotland, Stephanie Willemse.
A spokeswoman for Dressed to Kilt said: "The highly-anticipated event features kilted gents and plaid-clad ladies strutting their stuff down the runway for an A-list of judges.
"Traditional kilts as well as fashion-forward garb will be showcased in a lavish display of Scottish pride."
The organisers say Sir Sean Connery and his wife Micheline will be the official hosts for the event on 30 March.
Mike Russell, the culture minister, said: "Dressed to Kilt shines the spotlight on Scottish fashion and flair and creates interest in our talented designers within the North American market.
"I'm delighted that this year Dressed to Kilt, will showcase and promote Homecoming."