You need some sort of UI automation with which you can control a UI application such as Excel. Excel probably exposes some COM interface that you should be able to use for what you need. Python has the PyWin32 library which you should install, after which you'll have the win32com
module available.
See also:
If you don't necessarily have to work with Excel specifically and just need to do spreadsheet using Python, you might want to look at http://manns.github.io/pyspread/.