- Sam Sandwich (voiced by Wally Wingert): The main character, an anthropomorphic, bipedal, hero sandwich. He uses a wide array of gadgets to stop villains, such as jet boots, and his spaghetti blaster. He also has a sandwich sense, which allows him to detect evil.
- Salad Lad (voiced by Scott Menville): A broccoli-cherry tomato hybrid, Salad Lad is an inventor, and presumably made most of the inventions Sam uses in his fight against obesity. He has an inferiority complex, apparently, but little is delved into it. His voice sounds a lot like Robin from Teen Titans and Teen Titans Go!
- David (portrayed by Cade Cannon Bal): David is basically mission control for the team. He informs the pair of strange food-related happenings around town, which inevitably lead the two to one of four evil villains.
- Sweet Tooth (voiced by Cree Summer): A female antagonist with a cupcake for a head, she wants to make children eat only sweets. This antagonist is reminiscent of the witch from Hansel and Gretel. She has enormous lips (the pink color implies these are natural and not a consequence of lipstick usage), a southern drawl, a lanky, disproportionate body, a sinister grin, and polka-dotted skin (although maybe it's just a jumpsuit of some kind). She is a master of disguise and can throw bits of the frosting on her head to entrap foes. She may have been killed off at the end of "Sugar Chef", where she is frozen solid. Sam often refers to her as his nemesis.
- Big Cheese (voiced by Richard Steven Horvitz): An overweight, cheese-headed villain, Big Cheese likes to feed kids oversized food, and in large portions. Big Cheese wears a business suit and has a flying chair which he rides on, like a cross between a James Bond villain and Dr. Robotnik. He also sounds just like Kaos from Skylanders.
- Salty Pup (voiced by Richard Steven Horvitz): A dog pirate with beady eyes and a salt shaker for a peg leg, Salty Pup likes overly salted foods like pretzels. He does have a sword, and will use it, but Sam is simply a better swordsman than he is. He's also armed with cannons.
- Fryborg (voiced by Richard Steven Horvitz): Fryborg, contrary to his name, appears to be entirely robotic. He speaks with a stereotypical robot voice and mannerisms, and is the largest of the antagonists. His arms can change into a number of things to commit crime and attack the goodies with. Fryborg, true to his name, likes dishing out deep fried foods. Both of Fryborg's appearances have him short-circuiting. Fryborg can also shape shift into a truck. He appears to have missing teeth. These combined with his wide eyes, give him a dopey, non-threatening appearance.
The series was produced by Wholesome Productions, Inc. for Disney Junior. Dozens of Sam Sandwich faces were created for just one little series of 5-minute shorts, an incredible and dedicated feat.
- Lunch Candy: The menu at David's school is only advertising cotton candy and ice cream for lunch tomorrow!
- Lunch Truck Trick: A lunch truck is giving away free deep-fried food to kids in the park!
- Raining Fries: French fries are raining down all over the city!
- Sugar Chef: A new TV chef is persuading kids to add more sugar to all their food!
- Mega-Sized Menace: A mysterious beam from outer space has mega-sized David's breakfast!
- Sweet Water: Sweet Tooth is sweetening the city's water supply by pouring soda mix into the reservoir!
- Sam's Secret Weapons: David's local supermarket is selling deep-fried food instead of fresh fruit and vegetables!
- All You Can Eat: A new restaurant in town is only serving mega-sized meals!
- Buried Salty Treasure: A pirate chest crammed with salty snacks is buried in the sandbox!
- Salt Canon Caper: David's dinner is tasting super salty!