While I don't think this episode is amazing, I thought it was pretty good. It was pretty entertaining and interesting to see an episode focusing on Plankton and Sandy again. But the episode does have quite a few noticeable similarities to the episode from over a decade ago called Squid Defense. However, I think Single Cell Defense is different enough to be its own thing. But both episodes still have a lot of similarities.
First off, the titles between the episodes are quite similar. So unfortunately you can't help but make comparisons from the very start of the episode! But I feel like the rest of the episode isn't as similar as it might seem. One big difference is this episode focuses on Plankton learning self-defense to deal with people accidentally stepping on him, which is something he's been dealing with for the entire series! Squid Defense focuses on Squidward learning self-defense to protect himself against attackers or thieves. Both episodes do have Sandy teach them about Karate though. She even says to only use Karate for self-defense in both episodes. Then the characters (Squid and Plankton) go against this. But in this episode, Sandy never catches Plankton breaking her rule, unlike her catching Squidward in Squid Defense. So at least that's a difference between the episodes.
I thought the ending of this episode was somewhat weak though. Plankton isn't able to use his new Karate move on Mr. Krabs because he doesn't have feet. On one hand, I feel that is somewhat clever. But at the at the same time, I feel like Plankton could have still used the move on Krab's stubs. I don't see exactly why him not having feet would stop him. Maybe it would be a little more difficult, but I feel Plankton could have still used the move on him by grabbing his stubs. All in all, while this episode has quite a few similarities to Squid Defense, I feel it is different enough to mostly be its own thing and is a fun episode.