Gonzo has previously been classified as a "whatever," but after he begins to have disturbing dreams of abandonment, he begins to realize just how alone he is in the world. After an alien race appears to be trying to send him a message through his bowl of Kap'n Alphabet Cereal, Gonzo realizes that he may not be so alone after all and climbs to the rooftop to start watching the sky. His dreams are realized when he's hit by a bolt of lightning that serves as a conduit that allows him to communicate with a pair of Cosmic Fish, revealing to him that he is, in fact, an alien from outer space.
While Kermit and his friends refuse to believe his wild ravings, Gonzo is lured into the clutches of K. Edgar Singer (Jeffrey Tambor), a government agent who has also taken note of the aliens' attempts at communication and believes that Gonzo is his key to convincing his superiors that aliens do in fact exist. Kermit and the gang spring into action to rescue Gonzo, with the help of some handy inventions courtesy of Dr. Bunsen Honeydew and Beaker.
After a talking sandwich reveals to Gonzo the location of the eventual alien landing site, the Muppets (along with a crowd of alien-happy spectators) await their arrival. The ship comes to Earth and the aliens, who all look suspiciously like Gonzo, apologize for abandoning him but welcome him back to the fold. At first Gonzo considers going with them, until he realizes his true home is on Earth with his surrogate family and friends.
The Muppets' other feature films have been musical comedies. Following a different path, Muppets from Space uses a soundtrack of funk songs from the late 60s and 70s. One song is performed on-screen by the Alien Gonzos, and the Muppets sing a line of the opening song; otherwise, the songs function as a typical movie soundtrack.
The songs in the movie are:
- "Brick House" (The Commodores, 1977): The Muppets wake up at the boarding house, and prepare for their day.
- "Shining Star" (Earth, Wind & Fire, 1975): Struck by lightning, Gonzo travels through space to meet the Cosmic Fish.
- "Get Up Offa That Thing" (James Brown, 1976): Inspired by his otherworldly experience, Gonzo uses the lawnmower to mow a message in the lawn that can be seen from space.
- "Dazz" (originally performed by Brick, 1976): Gonzo hosts a hot-tub party on the patio for the alien relatives that he hopes will arrive soon.
- "Survival" (The O'Jays, 1975): Rizzo undergoes a series of uncomfortable experiments in the C.O.V.N.E.T. lab.
- "Getaway" (Earth, Wind & Fire, 1976): Having rescued Gonzo from the C.O.V.N.E.T. lab, the Muppets run through the hallways, avoiding the security guards.
- "Outa-Space" (Billy Preston, 1971): Gonzo and the Muppets arrive at Cape Doom to wait for the aliens to arrive.
- "Celebration" (Kool & the Gang, 1980): The Alien Gonzos greet their long-lost relative.
- "It's Your Thing" (The Isley Brothers, 1969): The Alien Gonzos celebrate their reunion with Gonzo by loading him into a cannon and shooting him into the air.
- "Flashlight (Spaceflight)" (originally performed by George Clinton, 1978): Clinton and Pepe the King Prawn duet on a special version of Clinton's hit "Flash Light" over the end credits.
- Muppet Performers
- Dave Goelz Steve Whitmire:Bill Barretta Jerry Nelson Brian Henson Kevin Clash Frank Oz Rickey Boyd John Henson Adam Hunt John Kennedy Peter Linz Drew Massey, Alice Dinnean Ed May Andy Stone Kim Allen Evy Berman John Boone Dennis W. Britt Tyler Bunch Lisa Consolo Rowell Gormon, BJ Guyer, Rob Killen Greg Jarnigan Jim Kroupa Bruce Lanoil Bob Lynch, Pamella O'Connor Tim Parati,Thom Stanley Lisa Sturz Mark Sutton, Allan Trautman Jay Tyson Gregg Wallace Uncredited: Kristina Donnelly Jodi Eichelberger Annie Peterle, Leslie Carrara Matt Yates Mary Harrison
- Human Cast
- Jeffrey Tambor as K. Edgar Singer
- F. Murray Abraham as Noah
- Rob Schneider as UFO Mania Producer
- Josh Charles as Agent Barker
- Ray Liotta as Gate Guard
- David Arquette as Dr. Tucker
- Andie MacDowell as Shelley Snipes
- Kathy Griffin as Female Armed Guard
- Pat Hingle as General Luft
- Hollywood Hogan as Man in Black
- Katie Holmes as Joey (uncredited)
- Joshua Jackson as Pacey (uncredited)
- Gary Owens as "UFO Mania" Announcer (voice, uncredited)
- Muppet Characters (speaking)
- Gonzo, Rizzo the Rat, Kermit the Frog, Miss Piggy, Fozzie Bear, Pepe the King Prawn, Animal, Bunsen Honeydew, Beaker, Bobo the Bear, Dr. Phil van Neuter, Ubergonzo, Robin the Frog, Clifford, Statler and Waldorf, the Swedish Chef, Scooter, Sweetums, Sam the Eagle, Sal Minella,, Johnny Fiama., Bean Bunny, Cosmic Fish, Bubba the Rat, Fast Eddie, Troy, Shakes, The Birdman, Dr. Teeth, Floyd Pepper and Carter,
- Background Characters (non-speaking)
- Janice, Zoot, Droop, Lew Zealand, Link Hogthrob., Beauregard, Rowlf, Marvin Suggs, Crazy Harry, Chip, Zondra, Zippity Zap, Baab the Sheep, Dr. Julius Strangepork, Chickens, Cows, Fish, Moose Head, Alexis the Giraffe, Lydia the Ostrich, Tommy the Thomson's Gazelle, Doreen the Camel, Penguins, Alien Gonzos, Balloon-Head Conductor, Custer the Bison, Monica the Musk Ox, D'kembe the Gemsbok, green monster from the meeting film "Think Bigger", Lobsters, Frackles, Flower-Eating Monster, Aretha, Begoony, Brool the Minstrel, Murray the Minstrel, Wander McMooch, Luncheon Counter Monster, Inkspots, The Newsman, Louis Kazagger, George the Janitor, Mildred Huxtetter,, J.P. Grosse, Slim Wilson, Zeke, Flash, Lenny the Lizard, The Fazoobs, Bill, Gil, Jill, Shakey Sanchez, Quongo the Gorilla, Butch the Tiger, Wolf,, Afghan Hound,, Koozebanian Phoob, Sprocket, Bill the Bubble Guy, Blustering Bellowpane Monster, Mudwell the Mudbunny, Poison Cackler, Beastie, Frankie the Wildebeest, Travis the African Buffalo, Randall the Zebra
- Photograph Characters (in gallery)
- In the 2009 and 2011 DVD releases, Jerry Nelson's lines for Statler are dubbed by Steve Whitmire:.
- In the 2009 and 2011 DVD releases, Jerry Nelson's lines for Robin the Frog, Floyd Pepper and Ubergonzo are dubbed by Matt Vogel.
- In the 2009 and 2011 DVD releases, Frank Oz's lines for Miss Piggy, Fozzie Bear, Animal and Sam the Eagle are dubbed by Eric Jacobson.
- In the 2009 and 2011 DVD releases, John Henson's lines for Sweetums are dubbed by Matt Vogel.
- In the 2009 and 2011 DVD releases, Adam Hunt's lines for Scooter are dubbed by David Rudman.
- In the 2009 and 2011 DVD releases, John Kennedy's lines for Dr. Teeth are dubbed by Bill Barretta.