Live Poll: Weirdest Sitcoms

You're heavy on animation even without Mr. Pickles, the demonic dog. For live action, consider Bosom Buddies.

Heil Honey certainly has the trippiest title.

Tsar,

For your consideration:

Mister Ed (1958–1966)
Mister Ed (Himself) is a horse who is owned by Wilbur Post (Alan Young). Mister Ed is not just any horse, he talks to Wilbur. But this gets Wilbur in all kinds of trouble because Mister Ed won't talk to anyone else, so Carol (Connie Hines), Wilbur's wife, thinks that Wilbur loves Mister Ed more then he loves her, because he spends so much time with Mister Ed. Mister Ed also talks on the telephone and goes out of his barn to cause mischief, for which Wilbur gets blamed.

My Living Doll (1964–1965)
A psychiatrist is given care of Rhoda Miller "real name 'AF 709'", a lifelike sophisticated but naïve android, which eventually learns how human society works and begins showing "or at least emulating" rudimentary emotions.

Mork & Mindy (1978–1982)
A wacky alien comes to Earth to study its residents and the life of the human woman he boards with is never the same.

3rd Rock from the Sun (1996–2001)
A group of aliens are sent to Earth, disguised as a human family, to experience and report life on the third planet from the sun.

Harry and the Hendersons (1987)
The Henderson family adopt a friendly Sasquatch but have a hard time trying to keep the legend of 'Bigfoot' a secret.

Hahaha, this is so funny (and what a good idea!). I haven't seen either of these but, just from the descriptions, I'm going to vote "My Mother the Car" or "Heat Vision and Jack." : )

In the question, I think it should say "has the trippiest premise?" (singular)

FYC: Greg The Bunny https://www.imdb.com/title/tt0280257/?ref_=nm_flmg_act_112

Tsar, it would be helpful if you included the premises in the descriptions.

  

Live Poll
https://www.imdb.com/poll/REeD8DybAIw/

A very raunchy honorable mention goes to the very difficult to find and uproariously hysterical, Interspecies Reviewers (2020– ). 

From elves to succubi to fairies and more, Our heroes: Stunk, a human, Zel, an elf and a hermaphrodite angel named Crimvael are here to rate the red-light delights of all manner of monster girls.

Basically, the plot revolves around a small group of adventurers as they go around town reviewing the many interspecific-run brothels. Definitely NSFW (even with the provided censor bars and such similar tactics).