With the assistance of her subordinate Junichirō Izumida, Ryōko works with her colleagues including her rival and fellow superintendent Yukiko Muromachi, alongside JACES security forces personnel and her personal maids Lucienne and Marianne, to investigate and resolve seemingly paranormal, supernatural or bizarre events that become involved in criminal cases—particularly when police procedures or modern science cannot be applied—before they go out of hand.

Because the novels, manga and the anime adaptations have different stories, paranormal events and creatures involved, their central plots are most of the time different from each other.

[a] Owned by the Yakushiji family, it's a security company that ex-police officers both enlisted and high-ranking are employed into after their retirement.

[1] In combat operations, they use PASGT ballistic helmets, gray BDUs, tactical vests and light to medium body armor.

[1] Its origins are traced back to the end of World War II when the "Japanese Empire Security Service" (大日本警備保障, Dai Nihon Keibi Hoshō) was established before it became JACES, which was supposed to be used for the basis of a restructured Japanese military before Ruriko went to create the JPP instead.

Known as the "Nippon Private Police" (日本私用警察, Nihon shiyo keisatsu),[b] it was founded by ex-Diet member Ryojun Tadomura and heavily funded by the Government of Japan to counter the influence of JACES in the domestic and international security market.

[4] They are known to be hired in war-torn countries after military forces are pulled back, conducting police duties in their place.

[6] During combat operations, JPP personnel are identified with green heavy body armor, anti-riot helmets and are armed with mostly Howa Type 89 assault rifles, Heckler & Koch MP5 and Minebea PM-9 submachine guns with expandable baton sticks.

[31][32][33] The series began in the May 2009 issue of Monthly Afternoon, published on March 25, 2009,[33] and it was renamed Yakushiji Ryōko no Kaiki Jikenbo: Kiri no Hōmonsha (薬師寺涼子の怪奇事件簿 霧の訪問者).

[35][36] A third series, titled Yakushiji Ryōko no Kaiki Jikenbo: Suiyobi ni Goyojin (薬師寺涼子の怪奇事件簿 水妖日にご用心), started in the March 2010 issue of Monthly Afternoon, published on January 25, 2010.

[43] A fifth series, titled Yakushiji Ryōko no Kaiki Jikenbo: Makyo no Jyoō Heika (薬師寺涼子の怪奇事件簿 魔境の女王陛下) was serialized in Monthly Afternoon from the February 2013 issue, published on December 25, 2012, to the November 2013 issue, published on September 25, 2013.

[58] The series began streaming in North America on RetroCrush as an exclusive title on November 5, 2021 under the name Ryoko's Case File.