This study aimed to assess the efficacy of Cynara scolymus (artichoke) leaf extract in the treatment of patients with functional dyspepsia. In a double-blind RCT 247 patients with functional dyspepsia were recruited and treated with two capsules of either 320 mg plant extract or placebo three times per day. The primary efficacy variable was the sum score of each patient’s weekly rating of the overall change in dyspeptic symptoms. Secondary variables were the scores of each dyspeptic symptom and the quality of life as assessed by the Nepean Dyspepsia Index. A total of 247 patients were enrolled, and data from 244 patients (129 active treatment, 115 placebo) were suitable for inclusion in the ITT analysis. The overall symptom improvement over the 6 weeks of treatment was significantly greater with C. scolymus (artichoke) leaf extract than with the placebo. Similarly, patients treated with C. scolymus leaf extract showed significantly greater improvement in the global quality-of-life scores compared with the placebo-treated patients.