Episodes follow Ebichu, a talking hamster devoted to her oft-indifferent owner, who is only identified as OL ("Office Lady"), a single 25-year-old (this is the age Japanese women are considered nearing the end of the ideal marrying age) who doles out cynical commentary and the occasional beating on the rodent. Ebichu tends to take this in stride with endless praise and compliments. Such abuse is usually caused by Ebichu's almost disturbing lack of tact or propriety, often embarrassing her master in front of other people.

Ebichu often attempts to correct OL's bad decisions, such as her berating of OL's obnoxious and untrustworthy boyfriend Ebichu nicknamed Kaishounachi (literally, Useless).