Miyu Suzuki is a high school girl whose cheerful outlook on life is tempered by her need to fit in. Coincidentally, beside her in the classroom sits Yuusuke Tani, a boy unconcerned with others' expectations. Their exchanges rarely extend beyond brief discourse, yet the polarity of their demeanors unexpectedly draws them to one another. As their mutual interest grows, the newfound feelings are no longer easy to ignore. Eventually, Suzuki voices what is inside her heart, forcing both of them to confront the unspoken affection between them. With each passing moment, their relationship evolves, and they gradually come to better understand themselves and the person who is their polar opposite.

At first glance, Galko, Otako, and Ojou are three high school girls who seem like they wouldn’t have anything to do with each other. Galko is a social butterfly with a reputation for being a party animal, even though she is actually innocent and good-hearted despite her appearance. Otako is a plain-looking girl with a sarcastic personality and a rabid love of manga. And Ojou is a wealthy young lady with excellent social graces, though she can be a bit absent-minded at times. Despite their differences, the three are best friends, and together they love to talk about various myths and ask candid questions about the female body. Oshiete! Galko-chan is a lighthearted and humorous look at three very different girls and their frank conversations about themselves and everyday life. No topic is too safe or too sensitive for them to joke about—even though every so often, Galko seems to get a bit embarrassed by their discussions!

After a school trip goes terribly wrong, Homare Onishima, Shion Kujou, Asuka Suzumori, and Mutsu Amatani are left stranded on a deserted island. While Shion, Asuka, and Mutsu are frightened and desperate, Homare seems strangely calm. Fortunately for the group, this isn't the first time she's been stranded! Homare spent her childhood training with her survivalist father all over the world, climbing cliffs, trapping prey, building shelters, and obtaining valuable nutrition from moose testicles. To Homare, surviving on an uninhabited island with a slim chance of rescue is child's play. The only problem is the other three. As Homare shamelessly guides her classmates through the finer points of survival, including drinking fish blood and eating cicadas, the girls start to realize that being stranded might not be as bad as they had imagined.

Self-professed home security guard Mahiro Oyama has not left his home in years, secluding himself in his room playing erotic visual novels. This depraved lifestyle causes his prodigious sister, Mihari, to worry about his well-being. In hopes of solving this problem, she devises a plan to rehabilitate him back to normalcy. The first part of Mihari's plan is to concoct a medicine that changes her brother's biological constitution into a bona fide female, much to Mahiro's vehement dismay. Stuck in this predicament, Mahiro has no choice but to live out his life as a cute girl until the effect wears off—if it ever does.