You're not comparing regex vs index, you're comparing a buggy and inefficient implementation of regex with a non-equivalent implementation using index.

• "(:?" should be "(?:"
• You compile the same regex repeatedly.
• You use captures where none are needed.
• The \s* is completely useless.
• You check if they key is the start of a word string with the regex solution, but not with the index solution.

Fixed:

use strict;
use warnings;

use Benchmark qw(cmpthese);

my @strings = (
    'Some string about this long or so, maybe this long',
    'I like pizza this long or so, maybe this long',
    'this long or so, maybe this French Fries long',
    'This Sugar Rush Rocks. maybe this do not stop the clock.',
);

my %hash = (
    'Sugar Rush Rocks' => 'whatever',
    'long'             => 'itsgood',
    'this long'        => 'ilikeit',
    'maybe this'       => 'itsokay',
    'Some String'      => 'loooveit'
);

my @keys_sorted_by_length_desc =
  sort { length $b <=> length $a } keys %hash;

cmpthese(-2, {
    Regex  => \&use_regex,
    Index  => \&use_index,
    Index2 => \&use_index2,
});

sub use_regex {
    my %re_keys = map { $_ => qr/\b\L\Q$_\E\b/ } @keys_sorted_by_lengt
+h_desc;
    for my $string (@strings) {
        my $s = lc($string);
        for my $key (@keys_sorted_by_length_desc) {
            if ( $s =~ $re_keys{$key} ) {
                #print "Found '$key' in '$string'\n";
                last;
            }
        }
    }
}

sub use_index {
    my @lc_keys = map lc, @keys_sorted_by_length_desc;
    for my $string (@strings) {
        my $s = lc($string);
        for my $key (@keys_sorted_by_length_desc) {
            my $lc_key = lc($key);
            my $spos = index($s, $lc_key);
            if ($spos >= 0 && ( $spos == 0 || substr($s, $spos-1, 1) =
+~ /\W/ )) {
                my $epos = $spos + length($lc_key);
                if ($epos == length($s) || substr($s, $epos, 1) =~ /\W
+/) {
                    #print "Found '$key' in '$string'\n";
                    last;
                }
            }
        }
    }
}

sub use_index2 {
    for my $string (@strings) {
        ( my $s = " \L$string " ) =~ s/\W/ /g;
        for my $key (@keys_sorted_by_length_desc) {
            my $lc_key = " \L$key ";
            if (index($s, $lc_key) >= 0) {
                #print "Found '$key' in '$string'\n";
                last;
            }
        }
    }
}
[download]

Results:

          Rate  Regex Index2  Index
Regex  23206/s     --   -33%   -56%
Index2 34824/s    50%     --   -35%
Index  53339/s   130%    53%     --
[download]

Update: Fixed many many problems.