A simple, fast, and low-cost method was developed to determine mefenamic acid in drug samples. Ultrasonic-assisted liquid-phase microextraction (UA-LPME) is applied to the preconcentration of mefenamic acid and subsequent detection by digital imaging colorimetry (DIC). The UA-LPME was performed with a eutectic solvent consisting of thymol and menthol (extraction solvent) and a solution of copper sulfate. Univariate optimization has been used to find the optimal working conditions. The variables studied were: copper sulfate concentration, eutectic solvent type, pH, sample volume, reaction time, and ultrasound time. The limit of detection obtained was 0.43 μg mL−1, and the precision (relative standard deviation) was 2.38%. The method was successfully applied to determine mefenamic acid in drug samples. The procedure follows the principles of green chemistry, as it uses small amounts of samples and reagents, generates few residues, and uses an environmentally friendly extraction solvent.