Ryan, Winnie the Pooh, Ash Ketchum, Littlefoot, Spongebob, Skipper, The Fantasy Adventure Team, Bobby, Cindy, Greg, Marcia, Peter, Jan, Oliver, Millicent, DJ, Stephanie, Michelle, Alex, Nicky, Malcolm, Mallory, Reese, Renee, Dewey, Daisy, Emily Yeung, Daniel Cook, the Jungle Adventure Crew, the Madagascar Crew, the cubs, Aladar, Taran, Jesse, Mikey, Bloom, The characters of Diary of a Wimpy Kid and the rest of the characters meet Dennis Mitchell (Justin Cooper) is finally back, and worse than ever. At the beginning of the movie, he goes over to Mr. Wilson's (Don Rickles) house to offer him one of several gifts for his birthday. These include lizards, snakes, bugs, and other creatures. This ordeal ends with Mr. Wilson unintentionally riding down a flight of stairs in Dennis' red wagon and accidentally getting his birthday cake thrown in his face by Martha (Betty White). Soon after this incident, Mr. Johnson, Dennis' grandfather (George Kennedy), shows up and announces that he is moving in with the Mitchells. Dennis starts spending more time with him than his annoyed neighbor. Mr. Wilson, upset that he's getting older, gets tricked by two con men (Brian Doyle-Murray and Carrot Top) who try to talk him into buying a "rare" root used to make tea to make people younger.Mr. Wilson is about to pay $10,000 when Dennis comes by. Dennis then reveals that he owns a root of the same kind, which he says he found on a place where those abound. Soon afterwards, the two impostors return and sell Mr. Wilson a machine that allegedly makes people younger. Suddenly, the attitudes of him and Mr. Johnson reverse as the latter feels George's pain of living in the same neighborhood as Dennis, while he starts to feel youthful and happy.While Dennis is trying to clean up a pile of garbage that he accidentally threw on Grandpa's car while he was taking out the trash, he accidentally destroys Mr. Wilson's machine. As a result of this, the Wilsons plan on moving away to be away from him for good, whereupon Mr. Johnson decides to move into their house, although no one seems to really want to carry out this plan.The film closes with Dennis helping the police (unintentionally) catching the con men, who were pretending to be several different workmen at the Wilson house when they were planning to move, attempting yet again to drain his bank account by stockpiling a hoard of his as yet unendorsed checks by claiming that the house needed several repairs before it could be sold. Dennis, who was a "menace" throughout the whole movie, ends up being a hero. The police return the uncashed checks, and Mr. Wilson decides not to move. Mr. Johnson, however, is now planning to move out of the Mitchell house because of everything Dennis, Ryan, Winnie the Pooh, Ash Ketchum, Littlefoot, Spongebob, Skipper, The Fantasy Adventure Team, Bobby, Cindy, Greg, Marcia, Peter, Jan, Oliver, Millicent, DJ, Stephanie, Michelle, Alex, Nicky, Malcolm, Mallory, Reese, Renee, Dewey, Daisy, Emily Yeung, Daniel Cook, the Jungle Adventure Crew, the Madagascar Crew, the cubs, Aladar, Taran, Jesse, Mikey, Bloom, The characters of Diary of a Wimpy Kid and the rest of the characters have put him through.
- Bobby, Cindy, Oliver, Greg, Marcia, Peter, Jan, DJ, Stephanie, Michelle, Malcolm, Mallory, Resse, Renee, Dewey, Daisy, Alvin, Simon, Theodore, Brittany, Jeanette, Elanor, Sarah Baker, Jake Baker, Henry Baker, Kim Baker, Jessica Baker, Mark Baker, Mike Baker, Lorraine Baker, Nigel Baker, Kyle Baker, Spanky, Stymie, Froggy, Porky, Buckwheat, Uh-Huh, Waldo, Mary-Ann, Jane, Darla, Alfalfa, Aldo, Ethan, Marissa, Bina, Ely, Otter, Lau, Mick, Naoko, Becky O'Shea & The Little Giants Gang, Tommy, Dil, Chuckie, Phil, Lil, Kimi, Angelica, Susie, Harold, Nicole, Z, Patty, Katie, Robby, Brian, Pepper, Molly, Duffy, Kate, July, Tessie, Vada, Thomas J., Dennis The Menace & Friends, Shake It Up: Camp It Up (Flynn and his friends), Casper, Wendy, Jazmine Payne, Carly Shay, Spencer Shay, Freddie Benson, Sam Puckett, Gibby, Nigel Baker, Kyle Baker, Mike Baker, Mark Baker, Jessica Baker, Kim Baker, Sarah Baker, Jake Baker, Henry Baker, Lorraine Baker, Cooper, Dylan Schenk, Ben Hilton, Jamie, Max, Becca, Nicky, Jeannie, The Flash/Tony, Crispin, Dylan, Duncan, Sean, Tony's Brother, Juel, Erin, Shirley Temple, The Barney & Friends and the Gang, German Speaking Boy, The Chipmunks (Alvin, Simon, and Theodore), The Chipettes (Brittany, Jeanette, and Eleanor), Aldo, Ethan, Miarissa, Bina, Ely, Otter, Tilly, Tom, Tiny, Ramona, Tina, Teddy, Denise, Derek, Harry, Rusty, Walter, Max, Sharkboy, Lavagirl, Linus, Marissa, Ely, Otter, Bindi, Rosie, Kelly, Lynn, Annie, Molly, Pepper, Duffy, Kate, July, The Fraggle Rock Gang, Andy, Ruby, Gracie, Kyle, Chyna Parks, Olive Doyle, Fletcher Quimby, Lexi Reed, Cameron Parks, Nat Wolff, Alex Wolff, Thomas Batuella, Allie DiMeco, David Levi, Qaasim, Cooper Pillot, Jesse Draper, Michael Jackson & Friends, Michael Jackson Badder, Spanky, Stymie, Froggy, Porky, Buckwheat, Uh-Huh, Waldo, Mary-Ann, Jane, Rascals #1, 2, 3, and 4, Friends of Stymie and Uh-huh, Darla, Alfalfa, Little Carbon Soldiers, Becky O'Shea, Junior Floyd, Jake Berman, Rudy Zolteck, Tad Simpson, Hanon, Marcus, Timmy Moore, Nubie, Johnny Vennaro, Briggs, Patterson, Priscilla O'Shea, Murphy, Keith, Marcus, Hector, Jessica, Lisa, Shock, Pete and Pete, Pablo, Tyrone, Tasha, Uniqua, Austin, Paul, The Oslen Twins, Calvin Cambridge, Murph, Ox, Marlon, Reg Stevens, Max Keeble, Megan, Robe, Kevin McCallister, Alex, Leah, Matilda, Penelope, Matthew, Dwayne, Steve, Robert, Nelly K., Sonny, Tawni Hart, Chad Dylan Cooper, Nico Harris, Grady Mitchell, Zora Lancaster, the Baby-Sitters Club gang, Simba, Nala, Timon, Pumbaa, Baloo, Kovu, Kiara, Uncle Max, Ma, Taran, Princess Eilonwy, Fflewddur Fflam, Gurgi, Jesse Greenwood, Elvis, Randolph Johnson, Nadine, The Goonies (Mikey Walsh, Brand Walsh, Mouth Devereaux, Data Wang, Chunk Cohen, Andy Carmichael, Stef Steinbrenner, and Sloth Fratelli), Scooby-Doo, Shaggy Rogers, Fred Jones, Daphne Blake, Velma Dinkley, Yogi Bear, Boo-Boo Bear, Snagglepuss, Huckleberry Hound, Quick Draw McGraw, Augie Doggie and Doggie Daddy, Wally Gator, Magilla Gorilla, Top Cat, Peter Potamus, Woody Woodpecker, Ttark, Toaster, Lampy, Radio, Blanky, Kirby, Fievel Mousekewitz, Tiger, Tony Toponi, Tanya Mousekewitz, Yasha Mousekewitz, Papa Mousekewitz, Mama Mousekewitz, Charlie Barkin, Itchy Itchiford, Hubie, Rocko, Jack Skellington, King Louie, Genie, Louis, Sebastian, Alex, Marty, Melman, Gloria, King Julien, Maurice, Mort, Roger Rabbit, and The Entire LionKingHeart Fantasy Films team and the rest of the characters will guest star in this film.