The episode starts at the Chum Bucket, where Plankton is searching for Spot. He finally finds a fat Spot and gives him a snack. Then, Karen comes to check Spot out, as she is wondering if Plankton is giving him too many treats. Plankton continues treating him well and Spot belches in front of him. Wanting to prove that the latter is still healthy, Plankton shows Karen its insides with X-rays, only to see that Spot is pregnant. Karen explains to him that food-rich environments such as the one Plankton provided to Spot causes amoeba's to reproduce. Plankton starts panicking, while Spot is generating other amoebas. Plankton is happy that Spot made it out fine and Karen starts smearing the new amoebas on her screen. However, she gets overloaded from so much cuteness, resulting in her getting damaged. While she is rebooting, Plankton tries to control them. The amoebas destroy various things in the lab, leading Plankton to attempt to get rid of them, as they can't hear him.
A happy SpongeBob is walking down the street, making bubbles in the form of an elephant and a caterpillar. When he sees a sign near the Chum Bucket saying "FREE AMOEBA PUPPY WITH ORDER OF CHUM," SpongeBob says hello to Plankton so he can see what's going on and Plankton tells him that he wants to sell Spot's puppies. SpongeBob offers Plankton to let him help have the puppies adopted.
At Barg'N-Mart, Plankton drives off two scouts and their bench with their biscuits so he and SpongeBob can make room for their business. SpongeBob suggests that Plankton start acting politely, but the latter doesn't seem to want to do so, evidenced by him making two of the Barg'N-Mart customers run away as fast as they can. Then, SpongeBob takes some of the amoebas, only to make a big puppy. Dave notices it and wants the puppy, so SpongeBob gives him one. A crowd of people are waiting to buy one, including Mrs. Puff, who remarks with how cute those amoebas are. SpongeBob makes, with the help of his body, more of them. However, things don't go quite positive, as an amoeba who is alone at Mrs. Puff's House starts destroying everything in their way, showing the consequences of leaving one alone.
Mrs. Puff's puppy comes to the Chum Bucket. Plankton sees that it has swallowed a pearl necklace from Mrs.Puff, which makes him call him a bad puppy. It is not late for him to notice that all the other puppies came back, each of whom having something from their owner swallowed. Plankton takes from the puppies all those things, as a theft. That of the Krabby Patty secret formula is now on his mind. He is about to start training them, but Karen is still rebooting, and Plankton finds it difficult to do that alone.
Plankton calls SpongeBob to train his pets. As soon as the training starts, SpongeBob shows them how to do innocent things, such as sitting and barking, while Plankton is shown at one of them how to do other things for evil purposes, such as opening a door and catching a grenade. After hours of training, Plankton introduces SpongeBob to the puppies: the Demolition Puppy, the Acrobat Puppy, the Identical Twin Puppies, and the Comic Relief Puppy. SpongeBob realizes that this has to do with the theft of the Secret Formula, and Plankton traps him inside a cage, while explaining the plan he has in mind:
Distraction with the Identical Twin Puppies inside the Krusty Krab.
The Acrobat Puppy goes inside Mr. Krabs' office and opens the window.
The Demolition Puppy goes inside Mr. Krabs' office from the window and opens with explosives into the safe, so it can take the formula.
The Comic Relief Puppy ends with a dollop of humor.
SpongeBob, although he doubts that this plan will work, doesn't know that this is actually what the puppies were doing all that time. While Plankton tries to open the bottle with the Secret Formula that the puppies gave to him after succeeding with the plan, SpongeBob throws with his tongue one of his eyes to Karen, which makes her fall down. Plankton goes to see what happened to Karen, and SpongeBob takes again the shape and form of an amoeba, whistles at the puppies and starts barking, so the puppies can do one of the tricks he learned to them during the training. The puppies end up freeing SpongeBob from the cage with switching a lever, and he takes away the formula from Plankton, who just raised Karen. SpongeBob decides to throw at him some treats, so the puppies can eat them and become bigger. The final size of them makes Plankton's restaurant blow up, with the formula rolling to Patrick, who is Mr. Krabs' pet in this episode. He gives the formula he found back to Mr. Krabs, who rewards him with a treat. Karen is now fully rebooted and looks at the amoebas on the floor of the restaurant as adorable again. She makes a maze of them, which results in a bigger amoeba, and the episode ends with it falling onto Plankton.