Salicornia herbacea is rich in natural minerals, dietary fibers, and potentially health-promoting phenolic compounds. In this paper, an experimental design was applied for the optimization of the ultrasound-assisted extraction of phenolic compounds from lyophilized Salicornia herbacea powder. The experiments were conducted in accordance with a five-level, three-variable central composite rotatable design (CCRD), and the effects of solvent concentration, extraction time, and extraction temperature were evaluated via response surface methodology (RSM). The optimal extraction conditions were as follows: ethanol concentration, 76.80%; extraction time, 20 min; and extraction temperature, $33.21^{circ}C$; and the solvent concentration was the most significant parameter in this process, under which the predicted total phenolic content was 49.91 mg GAE/g sample.