[Purpose] This study examined the effects of a medio-lateral unstable sole on invertor and evertor activation while descending stairs. [Subjects and Methods] The subjects were 30 university students with no history of ankle sprain. They descended stairs while wearing the medio-lateral unstable sole or with bare feet. Electromyography was used to record the activity of the tibialis anterior and peroneus longus and brevis muscles and paired t-tests were used to assess statistical significance. [Results] The medio-lateral unstable sole group showed increased tibialis anterior and peroneus longus and brevis muscle activation compared to the barefoot group. [Conclusion] Medio-lateral unstable sole can be used with exercises to prevent further ankle damage by activating both the inversion and eversion muscles.