Unfortunately, drama seemed to immediately follow the reboot, which was first "put on hold" by Disney in January, despite already filming two episodes.
Duff has now revealed that the "stars just didn't align".
"She has made such a lasting impact on many, including myself. To see the fans' loyalty and love for her, to this day, means so much to me.
"I want any reboot of Lizzie to be honest and authentic to who Lizzie would be today. It's what the character deserves."
Disney were able to get the entire McGuire original family on board for the series, which was a huge selling point for the reboot.
Actors Hallie Todd (Jo), Robert Carradine (Sam), and Jake Thomas (Matt) joined Hilary at a table read at the time, posing for a snap shared by Disney Plus last October.
Lizzie's good friend Gordo (Adam Lamberg) had also joined the cast.
The reboot series was going to follow a 30-year-old Lizzie making her way in New York City as an apprentice for a high-end decorator.
There was speculation about behind the scene's drama after Variety reported in February that the original series' creator Terri Minsky, who was on board for the reboot, had stepped away from the production over concerns it wasn't "family friendly".
At the time, Duff made a public plea to Disney saying it would be a "disservice" to fans if the show was PG, urging Disney to pass it onto their other streaming platform, Hulu.
"I feel a huge responsibility to honor the fans' relationship with Lizzie who, like me, grew up seeing themselves in her."
"It's important to me that just as her experiences as a preteen/teenager navigating life were authentic, her next chapters are equally as real and relatable."
Fans have expressed their shock and disappointment online after learning of the shows cancellation.
"I am genuinely so sad reading this, Lizzie is my whole life and I'm so gutted there won't be anymore of her," another wrote.