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.


There was an Emperor’s New Groove show and Kuzco is an adult
The Emperor’s New Groove is such a great movie. I actually mentioned watching it to my family a few days ago.
But yeah, cartoon characters in general are a bit of a toss-up, and their ages are hardly ever quite clear. I thought of all the Disney princess movies and decided to specify “live-action” in the title.