The name "Domo" was acquired during the second episode of his show in which a TV announcer said, "dōmo, konnichiwa" (どうも、こんにちは), which is a greeting meaning something along the lines of, "Well, hello there!", but which can also be interpreted as "Hello, Domo!", and thus is a convenient pun (dajare). The kun suffix on "Domo-kun," the name used to describe the character in the Japanese versions, is a Japanese honorific often used with young males.
Domo, the main character, is described as "a strange creature that hatched from an egg,"  with a large, sawtoothed mouth that is locked wide open. Domo's favorite food is Japanese-style meat and potato stew, and he has a strong dislike for apples, because of an unexplained mystery in his DNA. Domo can only communicate via producing a low-pitched noise which sounds somewhat like his own name, but other characters appear to understand him. Domo is known to pass gas repeatedly when nervous or upset. A Tokyopop press release of the Domo comic book states that "he communicates sotto voce with a verve that only his friends can understand." Clint Bickham, the writer of the Domo comic book, said that to him Domo's expression is "a sort of cheery wonderment. Like when a kid wakes to a room full of presents on Christmas day." While Domo's face has variants, to Bickham most of his expressions have "an underlying sense of fascination."
Domo lives in an underground cave with Mr. Usaji , known in Japanese-language versions as Usajii (うさじい), a portmanteau of the words usagi (うさぎ), (rabbit), and jii (じい) (old man, grandpa). Mr. Usaji is a wise old rabbit who has lived in a cave for decades, loves to watch television and drink astringent green tea. Mr. Usaji is not into any "new" materials, and does not own a telephone. In terms of fashion, Mr. Usaji focuses on materials instead of shapes. Mr. Usaji's favorite food is carrots, and his least favorite food is "something that is meaningless."
Also in the cave live two bats, a mother named Maya  (Shinobu (しのぶ) in the Japanese version) and her child Mario (Morio (もりお) in the Japanese version). Maya suffers from alcoholism; her favorite foods are seasonal while her least favorite food is alcohol. Mario's favorite food is Japanese-style tomato spaghetti, while his least favorite food is shiitake mushrooms.
The other main character in the shorts is a weasel girl named Tashanna  (Tā-chan (たーちゃん) in the Japanese version). Tashanna, 17 years old, is a weasel who aspires to be a fashion stylist or model in Tokyo and is always using technology (televisions, mobile phones, and cameras). In English Tashanna has a "weaselly accent" (いたちなまり itachi namari ) and ends her sentences with "y"s. In the Japanese version, she ends her sentences with "chi" (ち) . She has not had a boyfriend in ten years and she is seeking a platonic boyfriend. She has a passion for bidding in auctions, but she gives up by the end. Tashanna's favorite food is apricot and mint tarts, and her least favorite food is sea urchin. The Japanese name originates from the word "multichannel" (多チャンネル tachanneru ) of digital broadcasting.
Hee (Flower One (花一 Hanaichi )) and Haw (Flower Two (花二 Hanaji )) are pixie twins from a flower. Domo is the only individual who can see them.
The Fox Trio consists of Esther (Esuko (エスコ)), Brother Fox (あにきち Aniki-chi ), and Fox Boy (Konjirō (コンジロー)). Esther, the youngest member, enjoys producing crocodile tears, plotting schemes, and causing havoc. Brother Fox, the eldest member, dutifully cares for his youngest siblings and feels upset when referred to as "short-legged" (短足 tansoku ). Fox Boy, having a quiet demeanor, converses with Domo and Bear Boy and prefers to read.
Hungry Bear (はらぺこぐま Harapekoguma ), a large and powerful bear, feels too hungry to take advantage of his strength.
Tokyopop publishes Domo: The Manga, an original English-language manga series, in the United States and Canada. Clint Bickham created the stories and crafted the dialog; Bickam said that he did "pretty much everything short of drawing it." The stories were drawn by Rem, Lindsay Cibos, Jared Hodges, Sonia Leong, Maximo V. Lorenzo (in the special 7-11 edition only) and Erie Horita. Bickham decided to use a series of short stories instead of one long story to "recreate the feel of the original series," "so hopefully, reading a story from the manga will feel the same as watching an episode of the show." Bickham said that writing the stories became entertaining when he "got into the Domo mindset." The writer said that Domo's thoughts do not need to be expressed in words as they are "always very simple and innocent." Bickham added that sometimes other characters speak for him. Bickham said that the Domo: the Manga stories "are driven by situations instead of dialogue." To prepare for writing the series, Bickham watched each episode multiple times; Bickham intended to "get a feel for the characters so that the jump from stop-motion to manga would be as seamless as possible." He added that "more than anything, I had to have fun doing it. I don't think you can create a good Domo story without fun."
Domo became well known outside of Japan through a public service announcement that circulated on the internet depicting Domos chasing a kitten with the words stating "Every time you masturbate... God kills a kitten." An article from ICv2 stated "this phony PSA is quite out of character with Domo's image in Japan."
In 2006 Nickelodeon announced that it was to develop 26 two-minute shorts, Domo-kun for broadcast in the United States. In December 2007 ICv2 announced that Nickelodeon would begin airing the shorts in early 2008.
Target used the character as the theme of its 2008 Halloween promotions. This included a number of Halloween-themed products, such as candy and toys. An original animation was created for Target, available on its website.
A number of the Nickelodeon shorts were released on DVD in Region 1 as Domo Volume 1 in February 2010. This collection also includes the original NHK shorts, but the music in some has been changed, and the voices of all the characters besides Domo have been edited out. It is unknown whether this was a conscious choice by the distributor or whether this was accidental, but there are currently no plans to fix the problem.