The long-running zombie series is set to conclude in 2022 at the end of its 11th series.
Reedus, who plays Daryl Dixon, is set to feature in a spin-off of the series.
“Part of me is ready for a spin-off and ready for the excitement of what that will be and then another part of me is sort of in denial,” he said.
“I have been doing this for a while and it has become such a big part of my life, so it doesn’t really seem real.”
He added he is going to “miss the monsters” once the programme has ended.
“It has become such a big part of my life, this show, and Daryl’s become a huge part of my life,” Reedus said.
“I will definitely miss The Walking Dead universe.”
Reedus, 51, said he initially thought he would be in the programme “for an episode or two, and I was excited to do that”.
“I just wanted to be a part of it, I thought it would be fun,” he added.
The Walking Dead’s spin-off series will star Reedus and Melissa McBride, who plays Carol Peletier.
It is set to premiere in 2023.
Reedus said he is “curious” to find out “what the similarities will be and what the differences will be”.
He added: “I know there will be a lot of differences and I know the themes of the two shows are completely different, but the elements are kind of still there.
“I imagine I will see a zombie or two in the future.”
The Walking Dead premiered in 2010 and initially starred British actor Andrew Lincoln in the lead role as former police officer Rick Grimes.
Lincoln left the show during the ninth season.
The series already has multiple spin-offs, including Fear The Walking Dead and Chris Hardwick’s after-show Talking Dead.
