The development of less harmful cleaning methods, both for health and the environment, is one of the major concerns for conservators and restorers. Therefore, the possibility of replacing volatile and toxic organic solvents by ionic liquids (ILs) could contribute to safer procedures. Ionic liquids can be defined as organic salts with melting points below 100°C, constituted by an organic cation and an inorganic or organic anion. Some of the properties of ILs can be useful for the conservation of paintings. For example, their low volatility reduces the risks to health and the environment, their high viscosity may inhibit the penetration into the pictorial layers, and their adjustable miscibility with water or less toxic solvents (e.g., alcohols) allows their removal with safer solvents. This study evaluated the effects and consequences of possible cleaning operations with ILs. The effectiveness and risk evaluation was carried out through the application of different types of ILs in mock-ups prepared with various painting materials and varnishes.