You usually can't. On most operating systems, memory allocated to a program can never be returned to the system. That's why long-running programs sometimes re-exec themselves. Some operating systems (notably, systems that use mmap(2) for allocating large chunks of memory) can reclaim memory that is no longer used, but on such systems, perl must be configured and compiled to use the OS's malloc, not perl's.
However, judicious use of my() on your variables will help make sure that they go out of scope so that Perl can free up that space for use in other parts of your program. A global variable, of course, never goes out of scope, so you can't get its space automatically reclaimed, although undef()ing and/or delete()ing it will achieve the same effect. In general, memory allocation and de-allocation isn't something you can or should be worrying about much in Perl, but even this capability (preallocation of data types) is in the works.