It connects the small communities of Arlington and Plattsburg, along with MS 19, with the town of Noxapater.

The highway heads north through a mix of farmland and wooded areas for a few miles before crossing into Winston County.

The highway immediately passes through the community of Plattsburg, where it has an intersection with Plattsburg Road, which leads a short distance away to MS 25.

It winds its way northward through woodlands for the next several miles, crossing a couple of small creeks and having an intersection with Liberty Road (also leads to MS 25), before curving eastward to pass through farmland an enter the town of Noxapater along W Main Street.

MS 395 passes through neighborhoods before coming to an end at the center of downtown, at an intersection with MS 15 (Kilpatrick Street), with the road continuing east as MS 490 (E Main Street).