Background: Quinoa (Chenopodium quinoa) is a pseudo-cereal originally cultivated in the Andean region. The popularity of its seeds has increased in recent years due to the claims of health benefits and superfood qualities. Studies to date on the health benefits of quinoa have been restricted to animal models, and the results provide weak to moderate evidence to support improved plasma lipid profiles. Clinical trials in humans to examine the claims of health benefits of quinoa are limited to a few prospective studies and one randomized trial carried out in postmenopausal women. To our knowledge, no studies have been conducted in the general population. Objective: The objective of this randomized clinical trial was to investigate the effect of different quinoa doses (25 and 50 g/d) on body composition, serum lipids and hormones, and nutrient intakes in overweight and obese humans. Methods: This was a dose-response randomized, controlled, single-blind trial with a parallel design (1 control and 2 treatment groups) that compared the effect of 25 and 50 g quinoa/d in 50 overweight and obese participants over a 12-wk intervention period. Results: Body composition, nutrient intake, and total, LDL, and HDL cholesterol were not significantly altered by quinoa consumption (P > 0.05). Mean serum triglyceride (TG) concentration was reduced significantly in the 50-g quinoa group from 1.14 to 0.72 mmol/L at 12 wk (P < 0.05). The prevalence of metabolic syndrome (MetS) was also reduced in this group by 70%. No significant changes in TGs were observed in the control and 25-g quinoa groups. The prevalence of MetS was reduced by 40% (from n = 7 at baseline to n = 4 at 12 wk) in the 25-g group. Conclusions: The consumption of 50 g quinoa/d lowers serum TGs in overweight and obese participants and reduces the prevalence of MetS. This trial was registered at clinicaltrials.gov as UTN U1111-1175-470.