Been using CCleaner most every Sunday night to clean up files and the registry for a decade or more, I've never had a problem with it. I also use Defender and MWB.
As for slowing things down, don't have that either. I turned everything off once, Defender, MWB, Indexers (Windows, File Locator, and X1) - made no discernible difference to calibre performance, or any similar programs, made a bit of difference to large multi-file copies and moves. My data is on Sata III and USB 3 WD Caviar Black HDDs.
If the library is in Documents, it could be Protected Folders sticking its oar in, again.
BR
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