The arid climate in Southeastern Anatolia can quickly dry your skin, especially your hands, and especially if you have a sensitive skin and/or are normally living in a humid, coastal climate. So don't forget to pack along some kind of moisturizer if you intend to stay more than a few days in the region.
Being not accustomed to heavily spicy/hot food, in addition to the fact that some food are prepared in less than perfectly hygienic ways, may lead to stomach trouble in some travellers whilst in the region.
Stay abreast of the news in northern Iraq and southeastern Turkey before and during your visit to the region. The politics of the region is very fluid with the Turkish government threatening military intervention into northern Iraq and the Kurdistan Workers' Party PKK making raids on military outposts as well as attacking civilian targets like minibuses—though the situation is getting better and safer day by day. The Turkish military will sometimes declare security zones in the area, making civilian travel to the region impossible. It is often best to talk to fellow travelers in Istanbul, Ankara or, even better, Diyarbakir before making your way into the deep southeast. Don't trust the Istanbulites who will suggest that you won't live through any visit east of Ankara. A vast majority of them have never left Istanbul. A trip to southeastern Anatolia is very much feasible and, for the most part, safe. The deep southeast should be done with more caution, but it too is possible for the hardy traveler.
On some non-major routes, you may run into a few military checkpoints, though all you need to do is showing your passport therefore keep it handy during rides, not buried deep in your backpack. Keeping a short list of cities on your itinerary in mind may save time in case of further questioning at checkpoints.
talk
In Southeastern Anatolia, the Euphrates River Fırat forms some sort of linguistic boundary: west of the Euphrates is mostly Turkish speaking with a Kurdish-speaking minority while the mother tongue of most of the locals living east of the Euphrates is Kurdish. However, most locals in the region are also bilingual in Turkish, although heavily accented in most cases.
While traveling in southeastern Anatolia, it is important to be conscious of whom you are speaking with. At military checkpoints, Turkish and English will suffice most Turkish officers speak some English, usually due to previous training in the United States; it is critical not to test your smattering of Kurdish words with the Turkish military. When amongst Kurdish friends, the Kurdish language is appropriate, but be sure not to place your hosts in an uncomfortable situation by speaking in Kurdish while other Turks are present.
Arabic might also be useful as it is the mother tongue of many people living in the western and southern parts of the region, especially in and around Gaziantep, Sanliurfa, Hasankeyf, and Siirt. Syriac, also known as Assyrian, a direct descendent of Jesus Christ's mother tongue Aramaic, can also be heard spoken by small communities in and around Mardin and Midyat.
Many Arabic and Farsi expressions have made their way into the local vernacular.