Salinization of freshwater ecosystems is one of the major challenges imposed largely by climate change and excessive water abstraction for irrigated crop farming. Understanding how aquatic ecosystems respond to salinization is essential for mitigation and adaptation to the changing climate, especially in arid landscapes. Field observations provide invaluable data for this purpose, but they rarely include sufficient spatial and temporal domains; however, experimental approaches are the key to elucidating complex ecosystem responses to salinization. We established similar experimental mesocosm facilities in two different climate zones in Turkey, specifically designed to simulate the effects of salinization and climate change on shallow lake ecosystems. These facilities were used for two case-study experiments: (1) a salinity gradient experiment consisting of 16 salinity levels (range: 0–50 g/L); and (2) a heatwave experiment where two different temperature regimes (no heatwave and +6 °C for two weeks) were crossed with two salinity levels (4 and 40 g/L) with four replicates in each treatment. The experiments lasted 8 and 2 months, respectively, and the experimental mesocosms were monitored frequently. Both experiments demonstrated a significant role of salinization modulated by climate on the structure and function of lake ecosystems. Here, we present the design of the mesocosm facilities, show the basic results for both experiments and provide recommendations for the best practices for mesocosm experiments conducted under saline/hypersaline conditions.