The Canadian popstar won Favourite Male Singer, while Grande was honoured with Favourite Female Singer, and the former X Factor girl band collected the Favourite Group gong at the ceremony.
"Thanks for voting us favourite group at #KCA (Kids' Choice Awards)!! The experience was amazing. The slime was slimey. LOVE YOU!" Fifth Harmony later posted on Instagram.com, alongside a photo of themselves covered in the famous green goo.
Adele's smash hit Hello, which broke records when it was released late last year (15), was crowned Favourite Song of the Year.
Country star and The Voice judge Blake Shelton was on hand to host the awards show. His role didn't let him avoid being coated in the slime, however, and the ceremony at The Forum in Inglewood, California saw Blake coated along with Fuller House star John Stamos, Jason Sudeikis and Josh Gad.
Adam Sandler's Hotel Transylvania 2 nabbed the Favourite Animated Movie gong, while Star Wars: The Force Awakens won Favourite Movie.
Will Ferrell landed the top acting award for his role in comedy Daddy's Home, while Jennifer Lawrence was named Favourite Movie Actress thanks to her powerful portrayal of heroine Katniss in The Hunger Games movie franchise.
Amy Poehler was on hand to accept the gong for Favourite Voice from an Animated Movie for her role as Joy in Pixar's Inside Out, while Zendaya thanked parents across America for letting her be a role model to their children.
While on stage accepting her award for Favourite Female TV Star in a kids' show, she said, "Thank you for allowing me to be a role model for your children. I really, really do not take that for granted."
Blake was a huge success with his hosting duties, however his new girlfriend and fellow The Voice judge Gwen Stefani was unable to be there to support him as she had work commitments in Japan. Instead, the singer sent her two sons Zuma and Apollo to the ceremony to support her beau, and tweeted a photo of seven-year-old Zuma dressed up with his friends on the orange carpet.
Her youngest son Apollo was spotted in the audience on the phone to his mother, as she was having trouble live streaming the show while in Tokyo.
Robert Downey Jr. and Chris Evans also took to the stage during the awards ceremony to preview a new trailer for their upcoming superhero movie, Captain America: Civil War.
The Marvel film, due out in May (16), focuses on the feud between Captain America (played by Evans) and Iron Man (Downey Jr.). The pair joked onstage about ending their ongoing battle, and embarked on a thumb war in front of a cheering audience.
"Let's end this, once and for all," Evans challenged, but the wrestling battle ended in a draw, meaning fans will have to wait until they see the film, which also stars Scarlett Johansson, to see who wins the superhero showdown.
Kids' Choice Awards 2016, full list of winners
Favourite Movie: Star Wars: The Force Awakens
Favourite Movie Actor: Will Ferrell - Daddy’s Home
Favourite Movie Actress: Jennifer Lawrence - The Hunger Games: Mockingjay, Part 2
Favourite Music Group: Fifth Harmony
Favourite Male Singer: Justin Bieber
Favourite Female Singer: Ariana Grande
Favourite Song of the Year: Hello - Adele
Favourite TV Show: The Thundermans
Favourite Family TV Show: The Muppets
Favourite Male TV Star - Kids’ Show: Ross Lynch - Austin and Ally
Favourite Male TV star - Family Show: Jim Parsons - Big Bang Theory
Favourite Female TV Star - Kids' Show: Zendaya - K.C. Undercover
Favourite Female TV star - Family Show: Sofia Vergara - Modern Family
Favourite Talent Competition Show: The Voice
Favourite Cooking Show: Cake Boss
Favourite Cartoon: SpongeBob SquarePants
Favourite Animated Movie: Hotel Transylvania 2
Favourite Voice from an Animated Movie: Amy Poehler - Inside Out
Favourite New Artist: Shawn Mendes
Favourite Collaboration: See You Again - Wiz Khalifa feat. Charlie Puth
Favourite Book: Diary of a Wimpy Kid series
Favourite Video Game: Just Dance 2016