To open Outlook in safe mode, you can use the following steps. First, make sure Outlook is closed. Then, press and hold the "Ctrl" key on your keyboard. While holding "Ctrl," click on the Outlook shortcut or launch the application. A dialog box will appear, asking if you want to start Outlook in safe mode. Confirm your selection, and Outlook will open in safe mode, bypassing any potential issues caused by add-ins or customization.