When writing a book manuscript, what is the proper way to write something like Main Street? Is it OK to use Main St? If I use the abbreviation, is there a period after it?
You can, and it might be OK, but I'd reframe the question by asking why you would want to do that. Does it add something to the manuscript?
If you're writing in an intentionally less formal style, that might be the case. Otherwise, I would avoid it. No one is going to be put off by seeing "Main Street" when they would write it as "Main St.", but the reverse might not be true. Imagine someone reading the manuscript out loud. Could they read abbreviations as written rather than as intended? (This will depend on your audience.)
Also, be careful of ambiguity - particularly if the context doesn't make it clear. ("Who is this Main Saint you're talking about?").
In a manuscript, you generally don't want to use common abbreviations (i.e. 'w/' for with, 'add.' for additional, etc.) but it is okay to use abbreviations such as 'St.' for street. The main thing to keep in mind: if you would use the abbreviation when taking notes to simplify, don't use that abbreviation! But, if it is a common abbreviation like 'R.' for river or 'ave." for avenue, then that is perfectly fine.
This is a link to a Grammarly blog I found useful for when to use abbreviations.
I hope this helped! Happy writing. :)