There is really no way to force memory not to swap using a pure-Perl solution. This is something that is managed at the kernel level and is therefore very OS-dependent.

However, putting files in memory is possible in Perl, if you're using PerlIO (e.g. if you have perl >= 5.8.0). You can do this by:

open my $SRC, '<', $source_filename;

until (eof $SRC) {
   my $buffer;
   read($SRC, $buffer, 200_000);
   $memfile .= $buffer;
}

close $SRC;
open my $MEM, '<', \$memfile;

## now you can read from $MEM as a filehandle
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The above is example code only, there's a lot of error-handling and other considerations missing.

For a SQLite2 DB, you could attach to the database as a file, then attach to the special database :memory:, and use a couple of SQL statements to transfer the entire DB to RAM, then do all of your queries from there.

All of that said, don't be so sure you'll gain anything by doing this. Depending on what your real problem is (i.e. "why do you want this?"), you might be better off profiling your existing code and removing bottlenecks.