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Disabling non-webmail access restricts IMAP/POP3/SMTP access to the mailbox. Scripts and mail clients (like MS Outlook, Thunderbird, Apple Mail) using the IMAP, POP3, and SMTP protocols will no longer be able to connect to the mailbox. When the Non-Webmail access option is disabled, connections to the mailbox over IMAP/POP3/SMTP are not allowed. The mailbox can only to accessed via Webmail Classic and Roundcube. When combined with two-factor authentication, this can substantially increase the security of the mailbox.

Non-webmail access can be controlled per mailbox via the Mail Manager in the Control Panel:

Log in to the Control Panel, and go to the Mail Manager section. There, click on the Security button next to the mailbox in question. Hit the Disable button under the "Non-Webmail access" section. 

Control-Panel disable non-webmail access

To enable non-webmail access (i.e. allow connections over POP3/IMAP/SMTP) again, go to the same page and press the Enable button under "Non-Webmail access is disabled".

You can also disable and enable non-webmail access through Webmail Classic and Roundcube. Detailed instructions on how to do so are available in the Non-Webmail Access Control article.