The king of Slantania has officially appointed Sei Takanashi as the Holy Saint—an omnipotent maiden summoned from another world to save the kingdom. After months of relentless fighting against monsters, Sei can finally relax and continue her study at the Medicinal Flora Research Institute. Although her relationship with Albert Hawke, the commander of the Third Order of Knights, gradually blossoms, her bachelorette status attracts unwanted attention from other men—much to Albert's dismay. Moreover, Tenyuu—one of the many princes from the faraway Zaidera Empire—has taken an interest in Slantania and its powerful healing potions. Given that Sei's identity is a national secret, she must lay low in the royal palace until Tenyuu satisfies his curiosity at the institute and returns to his country. Despite his unimpressive appearance, the foreign prince is far from clueless. He has come to Slantania for a clear reason, and Sei's unique skills may just hold the answer to his cryptic research.

When Mizuki Hijiri transferred to a new school, all she wanted was to live a normal school life, but that did not prove to be the case when she met the infamous Hero Club. All of its members are boys suffering from various types of chuunibyou—Yamato Noda is a righteous hero, using his athletic abilities to perform noble deeds and protect others; Kazuhiro Nakamura claims to be the reincarnation of Touga Ryushouin, the result of the forbidden union between a demon and an angel; Tomoki Takashima is a pretty-boy otaku whose one true love is the 2D anime girl Sora; and Rei Tsukumo plays the role of a schemer, covertly pulling the strings. Dragged along as the newest member of the Hero Club, tepid Hijiri can't obtain the normalcy that she desires. But even so, despite their various quirks, their bonds of friendship are real; Hijiri's life can only get more exciting when she joins in on their delusions of grandeur!

During a regular after-school grub crawl, gluttonous high schooler Hibiki Sakura is confronted about her ever-expanding waistline by her best friend, Ayaka Uehara. With her attempts at solitary exercise failing miserably, Hibiki decides to join the newly opened Silverman Gym. At her orientation, Hibiki runs into student council president and school idol Akemi Souryuuin. However, it soon turns out that Hibiki is in for a lot more than she bargained for. Not only is Silverman Gym full of world-renowned bodybuilders and athletes, but to make matters worse, Akemi turns out to be a total muscle fetishist! Grossed out by the scene unfolding before her eyes, Hibiki begins to leave, only to be stopped by trainer Naruzou Machio. Completely enthralled with her newfound Prince Charming, Hibiki signs up as a gym member. Now, as a result of her spur-of-the-moment decision, Hibiki must adapt to her new lifestyle.

For centuries, Heaven has required its young angels to live and study among humans in order to become full-fledged angels. This is no different for top-of-her-class Gabriel White Tenma, who believes it is her mission to be a great angel who will bring happiness to mankind. However, Gabriel grows addicted to video games on Earth and eventually becomes a hikikomori. Proclaiming herself a Fallen Angel, she is apathetic to everything else—much to the annoyance of Vignette April Tsukinose, a demon whom Gabriel befriended in her angelic early days on Earth. Vignette's attempts to revert Gabriel back to her previous self are in vain, as Gabriel shoots down any attempt to change her precious lifestyle. As they spend their time on Earth, they meet two eccentric personalities: the angel Raphiel Ainsworth Shiraha, Gabriel's classmate with a penchant for sadism, and the demon Satanichia McDowell Kurumizawa, a clumsy self-proclaimed future ruler of the Underworld. Gabriel DropOut follows these four friends' comedic lives as they utterly fail to understand what it truly means to be a demon or an angel.