Open the file C:\Program Files (x86)\LibreCAD\resources\library\templates\empty.dxf
Set your preferred settings in Current Drawing Preferences and save the file.
Then, next time you open a new file, the settings are there.
empty.dxf is the default template, loaded when you start up LibreCAD.
Also, when you create a frame inside empty.dxf, you will always start with that.
You can have more templates e.g. for different paper size or orientation and use New From Template to open them.