The server could be something like Apache and mod_perl, or it could be something like POE::Component::Server::HTTP.

I use the Cygwin environment and the POE modules to interface to other programs this way. However, I wasn't able to get POE working well until a learned a fair amount of Perl. Maybe you will get lucky and find a POE example that is very close to what you need.

This might not be the 'absolute simplest' to develop, but after you get it working your code will be quite simple!

Yeah, I thought about using a server to handle the issue. The problem with this method is that, ideally, my finished application (excel sheet + custom VBA functions + working Perl scripts) is going to be transferred to other users, who are not even able to be considered n00bs. I'm trying to keep the techie overhead and the requisite configuration to a minimum so that I can just bundle up the necessary Perl directories in a .zip and send them along with my spreadsheet.

Instead of using a webserver, have your Perl script fork off its own server (if one isn't running at the time). It can communicate on a socket. We have a CGI program that keeps an large XSLT in standby. Using IO::Socket:

my $sock = new IO::Socket::INET ( LocalHost => $server,
                                  LocalPort => 9200,
                                  Proto     => 'tcp',
                                  Listen    => 2,
                                  ReuseAddr => 1,
                                );
die "socket creation error: $!" unless $sock;

while( my $client = $sock->accept() ) {
  binmode $client, ":utf8";
  $client->autoflush(1);

  # Read data
  while( $client->recv( $in_buffer, $buffer_size ) ) {
    # Store data
  }

  # Process data

  # Return data
  $client->send( $output );
}
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Some things to consider to make it dummy proof is allow it to adjust what port is runs on at runtime, and to have the server exit after a while to avoid zombie processes.