I have made the trip from Springdale to Ft Myers several times since my SIL lives in FT Myers and we have spent a few winters down there.
We usually drove through LR to Tallulah, LA to Vicksburg, Hattiesburg to Mobile. There are several areas of two lane and four lane non-limited access, with stop lights through towns. Highway 98 through Mobile can be frustrating sometimes. Have them take I-65 to I-10 if they go that way.
The last trip we went through Memphis, Birmingham, Montgomery, Dothan, to I-10. If they go this way take the I-55 bridge across the Mississippi River, rather than the I-40 bridge. This is the way I will go on future trips.
I don't really know much about Mcgehee except it is a small delta town. I doubt there is much crime, but I don't know that.
EDIT:
We stayed at the Best Western Dothan Inn & Suites the last time down. It was a decent safe motel. We only stopped once , but tend to drive for 10-12 hours a day.