A significant amount of the oil produced in Turkiye is extracted from the Southeastern Anatolia Region. In the drilling operations conducted around Batman and Diyarbakir, which are key areas for oil production in this region, formation-related problems are encountered, leading to increased drilling costs and time loss. The primary issues among these problems are the wellbore stability and the contamination of drilling mud with clay and calcium. In this study, experimental investigations were conducted in wells A-1, A-2, and A-3 located in region A, and well B-1 located in region B in the Batman and Diyarbakir areas. The investigations observed formation-related well stability issues and contamination of drilling mud with calcium and clay. Drilling mud experiments based on actual well data were conducted to address the changes in formation-related drilling mud. In wells A-1 and B-1, the drilling of formations containing gypsum and anhydrite was carried out using lignosulfonate mud, during which heavy calcium contamination occurred in the system mud, causing problems in the drilling operations. In well A-2, the drilling of gypsum and anhydrite in the Kayaköy formation, and shale and marl formations in the Kastel and Karadut formations, was done using KCl/Polymer mud. Experiments conducted on the drilling mud observed changes in the mud and examined the issues arising in the drilling operations. In well A-3, the drilling of rocks belonging to the same formations was performed, and lime mud was used in this well to counteract the possibility of gas influx, calcium contamination, and carbonate-bicarbonate contamination. The calcium concentration ranged from 120 to 800 mg/l in A-1 well, 80–800 mg/l in A-2 well, 440–680 mg/l in A-3 well, and 160–720 mg/l in B-1 well. Although calcium entrance to the drilling mud is inevitable during the drilling of calcium-bearing formation, this study shows that it is possible to drill these formations safely by the interventions at right times by the drilling fluid engineer.