The meaning of "You'd never guess ___" is "You would never know or guess ___ if someone didn't tell you." In other words, this isn't easy to guess on your own.
Here are some examples:
Look at this gorgeous pair of shoes! You'd never guess that they were only $30.
You'd never guess that she's 60 years old. She looks like she's in her 40s at most.
"You'd never guess" is followed by a clause, which is kind of like a sentence inside of another sentence. That clause is usually written in the past tense ("they were related" instead of "they are").
In written English or more formal speaking, you'd begin the clause with "that":
You would never guess that they were related to each other.
You can also use other words like "know" and "think" instead of "guess":
You'd never know that this neighborhood was once one of the roughest parts of town.
You'd never think that such a tiny amount of water could cause so much damage.