It’s where the word sinister comes from. In Latin it just means left, left hand side. Then in Medieval times the right got positive associations and the left negative which lead to left is bad then to evil. Hence sinister means evil. And why left handedness became associated with the devil.

I use both hands and their pronouns are those hands them hands

Makes you think about the word right, right?

Ned being shown as right handed while owning a store that caters exclusively to left handed people, is the joke within the joke. It's not that deep.

It shows Ned has a bit of shrewd business sense because he knows that lefties will more than willing to pay a premium to get left handed items. For example, I was willing to double the price to buy left handed scissors because it sucks to use "normal" right handed ones. Evidently, cutting stainless steel shim stock is hard on them and you can only resharpen them so many times. So I paid a lot of extra money to have a tool that I could comfortably use.