If you're doing this on Windows and can have Excel open, there's Spreadsheet::TieExcel. I haven't tried it. It looks a bit tricky compared to the Spreadsheet::(Parse|Write)Excel modules, which don't require you to be on Windows or to even own a copy of Excel.
There are several DBD backends to DBI that can deal with Excel or with CSV files. They will let you query and insert. However, unless your data fits the SQL idea pretty well that's an awkward way to solve it. DBD::Excel is the most obvious, and I've used it. It's not bad. It works directly on XLS files. DBD::CSV, DBD::AnyData, and DBD::RAM can all handle CSV files.
As moritz says, using Spreadsheet::ParseExcel and Spreadsheet::WriteExcel both should be neither difficult nor any major source of slowdown in your program.
In a more general theme, if you want to know what else is available to work with Excel files, you can always go to http://search.cpan.org and search for 'Excel'. It'll give you these results.
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