Is it possible to use the Saitek X52 joystick with Descent?
Out of the box, it doesn't work well. I haven't yet used the Saitek software to map the joystick buttons to keyboard keys, but I suppose that's next to try.

I'd say using something to map joystick buttons to keyboard buttons are your best bet. Either using the Saitek software you mentioned or Joy2Key.

You might also want to try a source port of descent such as D2x-xl. Along with other things, it improves joystick support, as it uses straight SDL instead of DOSBOX's SDL to fake DOS joystick. In fact DOSBOX would be your problem, while it is a great program, it doesn't support more than four buttons, and I'm not sure about rudder and throttle.

Hi! I was able to make my Saitek X-52 with Descent 1. You just wont get support for all the buttons.

Just configure the Controls inside Descent to use "Joystick" and customize the controls with "Customize Above".
You can set up to 4 buttons, and 4 axes. The rest will have to be trough the keyboard.

Calibrate both joysticks and you are good to go.

Don't bother creating joystick profiles