A single-use suppository insertion device includes a barrel, a plunger to be movably coupled to the barrel, and a disabling feature of the barrel or the plunger. The disabling feature may be activated during operational motion of the plunger relative to the barrel, such as during insertion of or withdrawal away from a suppository. The device can include a structural element of the barrel or the plunger to engage with the disabling feature of the barrel or the plunger during insertion of or withdrawal away from the suppository to activate the disabling feature. The disabling feature may be implemented in a number of ways to ensure single-use operation of the single-use suppository insertion device.