Defragmenting the disk while SQL Services are running is as safe as running defrag with the services stopped or on other, non database related data(*).
Windows own Defrag application, as well as pretty much all the alternatives, all use the file system defrag APIs built into the OS and file system, so there shouldn't be any great risk from defragging open files.
Your performance on that drive will take a serious hit, however, which might be worth thinking about depending on how responsive you need the database to be, as you're leaving it available, but that's about all you need to worry about.
(*) I wouldn't advise any major disk maintenance operations unless you had a backup, but of course you have a backup - it's your SQL database, right?