A vast number of our users have been asking questions about disabling Outlook signatures that, once CodeTwo Exchange Rules is on board, seem not to be important anymore. If you have thousands of users, asking them to switch Outlook signature off or (God forbid!) doing it alone one-by-one might do more harm than good.
However, you can use Group Policy Object, the tool for Exchange server, and disable adding all signatures created in Outlook. Step-by-step guide to disabling Outlook 2003 and Outlook 2007 signatures for Exchange users can be found in knowledge base in an article entitled: How to disable adding signatures created in Outlook for Exchange users
See also:
How to disable adding signatures created in OWA for Exchange users
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How can I do this for Office365 users who use Outlook on desktop?
This guide applies to Office 365 users as well, at least as long as they are on Windows Server.
If not, then you can manually change certain registry values (you can find out which in this article).