Learning about Mr. Osomatsu's second season, the sextuplets of the past decide to see how they've turned out in the future.

The brothers are pressured by their parents to find a job, the siblings try their hand at internet streaming, only to get flagged for their inappropriate actions. Later, Iyami uses an experimental detergent made by Dekapan to keep his suit clean for a party. However, it ends up getting drunk by the siblings, causing them to turn invisible down to their organs. As a result, they attempt to paint each others bodies, becoming upset that noone notices anything different about them.

Being the only two alone in the house, Choromatsu and Ichimatsu struggle to make conversation with each other. Later, Totoko takes part in an eating contest but keeps getting distracted by the brothers getting attention from the celebrity MC, Shōei.

Noticing Matsuzou acting strangely, the siblings discover that he is worried that there's not enough spark in his marriage with Matsuyo. Feeling he should return to a more innocent time, the boys give Matsuzou a masterlcass in being a virgin, albeit with no success. Matsuzou inevitably resorts to getting a love potion from Dekapan, but ultimately decides against using it, managing to sort things out with Matsuyo by himself.

A series of summer-themed skits. Jyushimatsu takes part in radio exercises, Iyami and Chibita try to beat the heat, Todomatsu keeps finding himself exiled by his brothers, Karamatsu tries to inject summer into everyone's lives, and the sextuplets attempt to talk to girls on the beach.

Iyami goes to sextuplets for help after falling on hard times and Hatabou searches for a friend.

In a parody of Romance of the Three Kingdoms, Emperor Osomatsu and a group of bizarre generals attempt to take over the country. Meanwhile, in the real world, Osomatsu joins Todomatsu at a mixer, struggling to keep his perverted instincts in check.

Dayon uses Dekapan's latest invention to merge various people together into new beings, with a fiendish end goal in mind. Jyushimatsu becomes determined to get a job at a sea park as an actual dolphin, receiving strict training from a female trainer. Meanwhile, Totoko and Nyaa encounter each other at Chibita's oden stand.

Ichimatsu struggles to get any sleep with his brothers being noisy all night and refusing to turn off the light. Unable to take anymore, Ichimatsu starts monitoring the brothers' courtesy towards each other, leading Osomatsu to get criticized the most. Later, Iyami proves his skills at the arcades by playing games at their highest difficulty.

Karamatsu tries to take on various requests from everyone to look like a reliable brother, only to take on more than he can handle, so Choromatsu tries to teach him how to refuse. Totoko begins working at a company, proving to be a handful for her superior Todomatsu. Later, a pair of seiyuu attend a dubbing session of an episode of Mr. Osomatsu, witnessing how the sextuplets do their work.

Already angered over the siblings gambling instead of paying off their oden tab, Chibita vows revenge on them after they pluck out his one-and-only hair. That night, Chibita begins taking out the siblings on by one, shaving all of their hair and stuffing oden in their faces.

Jyushimatsu befriends a young boy named Eitarou but gets called in by Eitarou's mother when he starts imitating him. Contrary to Jyushimatsu's fears, however, she asks him to teach Eitarou jokes so he can make friends at school. Later, Dayon steals Dekapan's underwear, forcing him to give chase all over the city while butt naked.

A series of end-of-year skits. Osomatsu and Choromatsu try to do one thing that could make them say they had a good year. Ichimatsu gets persuaded to take part in a lottery, Dekapan and Dayon pound mochi together, Hatobou gets pestered by some greedy Jizou statues, Choromatsu sends some untruthful New Years' cards. Todomatsu is fired from the Matsuno family and is forced to try out for a reserve team.

Sanematsu wakes up in Osomatsu's world as the seventh Matsuno brother. After spending several weeks of happiness with the siblings, Sanematsu eventually realises it was all a delusion he had been experiencing after ending up in a car accident. Jyushimatsu, Iyami, and Hatabou go on an expedition to find a Super Mongolian Death Worm. Choromatsu changes up his image by dying his hair brown, making it hard for his brothers to tell him that it's doesn't actually make him look cool.

The brothers struggle to remove the lid off of a particularly stubborn jar. Karamatsu runs his own taxi service, proving to have no idea what he is doing when he picks up an office lady. Finally, Totty holds a quiz for his brothers, containing several questions without right answers.

A group of aliens pursue the legendary space pirate, Shazarr. Displeased with Chibita's oden, Matsuzou serves up his own brand of oden, only for noone to show up. Later, the sextuplets become enamored by their new neighbor, Kinko Inuyama, prompting jealousy from Totoko when they go on a date with Kinko instead of her.

Ichimatsu becomes paranoid when lucky things happen to him all day, so he and Jyushimatsu try to punish themselves to balance things out. A lovey-dovey couple go to a hot spring inn that's haunted by a zashiki-warashi named Osoma.

Iyami comes across a blind flower girl named Okiku and, despite being poor himself, tries to help her raise money for eye surgery. Failing to win a wrestling match due to interference from Chibita, who develops a crush on Okiku, Iyami begins working an earnest living to raise the money. With Iyami still falling way short of the surgery bill, Chibita tries to give the remaining money under the pretense of a robbery, only to wind up getting him implicated as an actual robber. However, the rest of the town comes to Iyami and he manages to get the money over to Okiku before he gets caught. Years later, after finally being released from prison, Iyami is relieved to see Okiku now living a normal life as a florist.

After Dekapan becomes president, his secretary Todomatsu tries to keep him from pressing the Big Red Button. Iyami attempts to pull off a sham ventriloquism scheme by having Chibita and Hatabou act as his puppets. On Valentine's Day, the brothers try in vain to get some Valentine's chocolate from someone.

Yet another collection of random skits. Chibita tries selling some sextuplet meats buns, Choromatsu files his taxes, Osomatsu accuses his brothers of stealing his wallet, a fierce wave of pollen hits town, Totoko tries to escape a creepy maze, Jyushimatsu becomes a raccoon, Todomatsu tries doing something crazy, kindergartners visit a bread factory, the Proper-Rangers prepare to set off, and Osomatsu takes part in a skeleton event.

The brothers get rowdy while getting drunk at a restaurant. Unemployed office lady Totomi ends up taking a job at a strange establishment that offers some peculiar services. After being visited by a salesman, Matsuyo contemplates sending off one of her sons to a NEET correctional facility, asking Choromatsu to help her decide which one to send away.

Osomatsu and his friends decided to go on an overseas trip by Hatabo's plane. However, the plane crashed on the way, and I arrived at the place ...

A common scene after a drinking party. Osomatsu and others are sloppy at Ramen Himatsuya. The second. / The life of Dayon, which has been a mystery until now, is revealed! !! And another Dayon appears in front of Dayon! ?? / Recently, Iyami who has lost confidence in doing Osomatsu-san. I consulted with the program producer, but ... / A common scene after a drinking party. Osomatsu and others are sloppy at Ramen Himatsuya. 3rd.

Matsuzou becomes hospitalized, leading the brothers to seriously think about their lives and get proper jobs to support their family. As Osomatsu starts to find this new life boring, Totoko encourages him to think for himself.

Osomatsu's big announcement to his brothers is interrupted when Iyami crashes a plane into their house, killing them all and sending them to the underworld. Brought before King Enma, the brothers fail to come up with a good reason why they should go to Heaven and ultimately wind up in Hell. Just as the brothers realize they are still virgins, Totoko and the others, aided by the spirit of Fujio Akatsuka, dive into Hell to bring them back. Receiving further help from other dead allies, the brothers manage to escape Hell and return to life, although they are not exactly happy with the state of their bodies.