Instead of the join, try slurp mode. See local and $/ (the latter might be in perlvar.

Instead of using s///, try tr///. It's more efficient.

Always check the return values of system calls, like open. An array in scalar context gives the number of elements.

my $file;
my $out = 'wordlist.txt';
{
    local $/;
    $file = <>;
}
$file =~ tr/\n / /s;
$file =~ tr/A-Za-z0-9 //dc;

my %wordlist;
$wordlist{$_}++ foreach (split ' ', $file);

open(LIST, ">$out") or die "Can't open $out: $!";
print LIST join("\n", keys %wordlist);
close LIST;
print (scalar keys %wordlist), " words found.  Saved in $out\n";
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That's untested, but that's how I'd do it. (Minus any bugs, of course.)

Update: Removed the problematic /d switch from the first tr/// statement, prompted by turnstep's defense of his more comprehensive post.