grep -G '#.*' file

text

text
    #comment

changed text
    #comment

$ # comparing files with comment-only changes
$ diff -u -I '#.*' test{1,2}
$ # comparing files with both comment and regular changes
$ diff -u -I '#.*' test{2,3}
--- test2       2011-07-20 16:38:59.717701430 +0200
+++ test3       2011-07-20 16:39:10.187701435 +0200
@@ -1,2 +1,2 @@
-text
+changed text
 #comment

diff -u -B <(grep -vE '^s*(#|$)' test1)  <(grep -vE '^s*(#|$)' test2)

diff -b -I '^#' -I '^ #' file1 file2

diff -u -B <(sed 's/^[[:blank:]]*#.*$/ /' file1)  <(sed 's/^[[:blank:]]*#.*$/ /' file2)

File test1:
  text
  #comment
  other text
File test2:
  text
  new line here
  #comment changed
  other text changed

$ echo -e "#!/usr/bin/sed -fns/^[[:blank:]]*#.*$/ /" > outcom.sed
$ echo "diff -u -B <(./outcom.sed $1)  <(./outcom.sed $2)" > mydiff.sh
$ chmod +x mydiff.sh outcom.sed
$ ./mydiff.sh file1 file2 > file.dif
$ cat file.dif
--- /dev/fd/63  2014-08-23 10:05:08.000000000 +0200
+++ /dev/fd/62  2014-08-23 10:05:08.000000000 +0200
@@ -1,2 +1,3 @@
 text
+new line

-other text
+other text changed

$ patch -p0 file1 < file.dif
patching file file1
Hunk #1 FAILED at 1.
1 out of 1 hunk FAILED -- saving rejects to file file1.rej

$ echo "diff -B <(./outcom.sed $1)  <(./outcom.sed $2)" > mydiff.sh
$ ./mydiff.sh file1 file2 > file.dif
$ cat file.dif
1a2
> new line
3c4
< other text
---
> other text changed
$ patch -p0 file1 < file.dif
patching file file1
$ cat file1
text
new line
#comment
other text changed

egrep -v "^$|^[[:space:]]*#" /path/to/file

sed -e '/^#.*/d' -e 's/#.*//g' | cat -s