If you include non-humans, then Stan from Dog with a Blog is the second adult protagonist, albeit a dog.
*Raven’s Home stars Raven-Symoné as an adult in-canon, but I’m reluctant to include it since it is a spin-off of Raven’s teenage character in That’s So Raven.
If you accept movies and works where there is a shared protagonist role, then you could count Freaky Friday and I assume its spin-offs.
Apparently there was almost a show about Arwen from Suite Life of Zack and Cody but Disney passed on it in favour of Wizards of Waverly Place
Acceptable decision