In an alternate reality where alien invaders known as the Amanto have conquered feudal Japan, swords are banned and samurai have lost their place in society. Gintoki Sakata, a wild-haired silver samurai with a sweet tooth and no desire to follow the rules, runs a freelance odd-jobs business called the Yorozuya. He is joined by Shinpachi Shimura, a kind-hearted boy with glasses who often serves as the straight man, and Kagura, a super-strong teenage girl from the alien Yato clan who has an endless appetite. Together with their giant dog Sadaharu, they take any job to pay the rent, which somehow never gets paid.

The fourth season, which aired 51 episodes from April 2009 to March 2010, continues the series' signature blend of chaotic comedy, pop culture parodies, and sudden shifts into heartfelt action. The Yorozuya find themselves in absurd situations, such as accidentally ruining the Shogun's hairstyle at a barber shop, competing in a high-stakes race to become the official fan club for pop idol Terakado Tsu, and dealing with a mayonnaise-obsessed police officer named Toshiro Hijikata who gets handcuffed to Gintoki.

Several major story arcs unfold during this season. In the Red Spider arc, Gintoki and Tsukuyo, the guardian of the lawless red-light district Yoshiwara, confront a legendary assassin named Jiraia. Jiraia is Tsukuyo's former master who trained her in the brutal arts of the shadow warriors, but his twisted devotion now threatens to destroy her and the city. The arc delves into Gintoki's past and his own relationship with his mentor, revealing painful memories that have shaped who he has become.

The season also features the Popularity Poll arc, where the characters react to the results of an official fan ranking in a typically meta and self-destructive fashion. The Otsu-chan arc sees Hijikata and Shinpachi face off in a bizarre trading card battle tournament to decide the fate of their favorite idol's fan clubs, while a computer virus infects the robot maid Tama, forcing the Yorozuya to enter her digital world to fight the infection.

Later episodes introduce the Onmyoji arc, where the weather forecaster Ketsuno Ana is revealed to come from a family of traditional spirit users, and her accurate forecasts are being sabotaged by rival sorcerers. The season concludes with a Christmas-themed contest where multiple characters dressed as Santa Claus compete to prove who is the real one, ending on a surprisingly warm note as Kagura wishes everyone a merry Christmas.

Throughout the season, the Shinsengumi police force remains a constant presence, with commander Kondo Isao, the sadistic Sougo Okita, and the mayonnaise-loving Hijikata often clashing or reluctantly cooperating with the Yorozuya. The terrorist-turned-fugitive Kotaro Katsura and his mysterious pet-like companion Elizabeth also appear frequently, adding to the chaos. Two opening themes are used: Stairway Generation by Base Ball Bear for the first half, and Light Infection by Prague for the latter half, along with four ending themes. The season balances episodic comedic adventures with longer, more dramatic arcs that explore the characters' pasts and the growing threats to Edo, setting the stage for the increasingly serious conflicts to come.