The documentation of Workbooks.Open says:
By default, macros are enabled when opening files programmatically. Use the AutomationSecurity property to set the macro security mode used when opening files programmatically.
This works for me:
use warnings;
use strict;
use Win32::OLE ();
use Win32::OLE::Const 'Microsoft Excel';
$Win32::OLE::Warn = 3; # die on errors
my $Excel = Win32::OLE->new('Excel.Application', 'Quit') or die "Faile
+d to open Excel";
# or to get running Excel instance: Win32::OLE->GetActiveObject('Excel
+.Application')
my $const = Win32::OLE::Const->Load('Microsoft Office '.$Excel->{Versi
+on}.' Object Library');
$Excel->{AutomationSecurity} = $const->{msoAutomationSecurityForceDisa
+ble};
$Excel->{Visible} = 1;
my $Book = $Excel->Workbooks->Open("filename.xlsm");
$Book->Activate;
# ...
$Excel->Quit;