I've been to De Smet and loved touring the Laura Ingalls Wilder sites and memorabilia. However, I think you can pretty much do it in a day. If you plan to head up I-29 to Fargo and into MN, I would consider a stop at the Terry Redlin Museum right on the interstate at Watertown, SD. I would also consider
the Hjemmkomst Center in Moorhead, MN. Are you planning to visit the headwaters of the Mississippi at Itasca State Park in MN? Late September would be a beautiful time to see the fall colors!

If you are going on up to ND from DeSmet, consider taking US 81 from Arlington up to Watertown. It is (a little) more scenic that I-29.