Blair Slater || Bartholemew "Bart" James || Shirley and Bo's nerdy friend || colspan="4" style="background:#e0ffff; text-align:center;"| Main |- | Brendan Fletcher || Sterling "Stink" Patterson || Shirley and Bo's easygoing friend. Sebastian Moran counterpart || colspan="3" style="background:#e0ffff; text-align:center;"| Main || colspan="1" style="background:#ececec; color:gray; vertical-align:middle; text-align:center;" class="table-na"| |- | Chris Humphreys || Robert Holmes || Shirley's father || colspan="4" style="background:#e0ffff; text-align:center;"| Main |- | Elizabeth Shepherd || Peggy Holmes || Shirley's grandmother || colspan="3" style="background:#e0ffff; text-align:center;"| Main || colspan="1" style="background:#ececec; color:gray; vertical-align:middle; text-align:center;" class="table-na"| |- | Marie Stillin || Ms. Cynthia Stratmann || Headmistress of Sussex Academy || colspan="4" style="background:#e0ffff; text-align:center;"| Main |- | Colin Fox || Mr. Arthur Howie || Sussex History Teacher || colspan="4" style="background:#e0ffff; text-align:center;"| Main |- | Maggie Huculak || Dr. Joanna Holmes || Shirley's mother|| colspan="2" style="background:#ffe4e1; text-align:center;"|Recurring || colspan="2" style="background:#e0ffff; text-align:center;"| Main |- |} Main characters Meredith Henderson as Shirley Holmes: The great-great-niece of Sherlock Holmes, Shirley is the daughter of British diplomat Robert Holmes and virologist Dr. Joanna Holmes. She carries on her famous ancestor's legacy of solving crimes through deductive reasoning while attending the prestigious Sussex Academy. In addition to Sherlock's detective skills such as deductive reasoning and disguise, she also has his mannerisms, but she can still express her emotions. She prefers to keep a low profile so she can continue her sleuthing. She wears a variety of hats throughout the series. John White as Francis Boris "Bo" Sawchuk: Shirley's sidekick. An ex-gang member from a Ukrainian family, Bo attends Sussex Academy on a scholarship. He first met Shirley in afterschool detention and was amazed at the girl detective's deductions about him. Shirley came to his aid after he was falsely accused of setting a work shed on campus on fire. After that case was solved, Bo became her sleuthing partner and best friend, akin to the relationship between 'Sherlock Holmes' and 'Dr. Watson'. He was supposed to be colorblind in first episode however that was never mentioned again. Bo is commonly mistaken as Shirley's boyfriend. His first appearance was in "The Case of the Burning Building." At the end of the series, he leaves for Ukraine to further his studies. Sarah Ezer as Molly Hardy: Shirley's nemesis, and Moriarty counterpart. A newcomer to Sussex Academy, Molly first appeared as Alicia Gianelli's running mate during the school election for student council president. Through an elaborate scheme, Molly is elected student council president.