Medenine sits on the main road from Gabes (75 km north) to the Libyan border and Tataouine, and on the route to the island of Jerba to the east. There is no train station; long-distance buses and louages run frequently from Gabes, Tataouine (45 minutes south), Jerba (90 minutes east), and Tunis (around 8 hours north).
The bus and louage stations sit on opposite sides of the town centre. For local trips to Metameur, Ksar Hadada, Chenini, and other nearby villages, you will need to hire a taxi for the day or rent a car. A few of the larger hotels in Tataouine and on Jerba arrange day trips that take in several ksour and pass through Medenine.