OBJECTIVE To compare the postprandial and overnight glycemic response using a novel green aquatic plant thought to provide a dietary source for high-quality protein, with an iso-carbohydrate/protein/caloric dairy shake. RESEARCH DESIGN AND METHODS This is a randomized controlled crossover trial among 20 abdominally obese participants (age 51.4 years; fasting plasma glucose 110.9 mg/dL), who were allocated to replace dinner with either, first, a green shake containing Wolffia globosa duckweed (Mankai: specific-strain) or an iso-carbohydrate/protein/calorie yogurt shake. A 2-week flash glucose-monitoring system was used to assess postmeal glucose dynamics (6 net administration days; 97 observation days in total). We further obtained from each participant dietary/daily activity/satiety scale/sleep logs. Participants were recruited from the green-Mediterranean diet arm of the 18-month Dietary Intervention Randomized Controlled Trial-Polyphenols Unprocessed (DIRECT-PLUS) study. RESULTS Wolffia globosa Mankai elicited a lower postprandial glucose peak compared with yogurt (∆peak = 13.4 ± 9.2 vs. 19.3 ± 15.1 mg/dL; P = 0.044), which occurred later (77.5 ± 29.2 vs. 59.2 ± 28.4 min; P = 0.037) and returned faster to baseline glucose levels (135.8 ± 53.1 vs. 197.5 ± 70.2 min; P = 0.012). The mean post–net incremental area under the curve (netAUC) was lower with Wolffia globosa up to 60 and 180 min (netAUC 60 min: 185.1 ± 340.1 vs. 441.4 ± 336.5 mg/dL/min, P = 0.005; netAUC 180 min: 707.9 ± 1,428.5 vs. 1,576.6 ± 1,810.1 mg/dL/min, P = 0.037). A Wolffia globosa–based shake replacing dinner resulted in lower next-morning fasting glucose levels (83.2 ± 0.8 vs. 86.6 ± 13 mg/dL; P = 0.041). Overall, postprandial glucose levels from the shake administration until the next morning were lower in the Wolffia globosa Mankai green shake compared with the yogurt shake (P < 0.001). Overnight sleep duration was similar (378.2 ± 22.4 vs. 375.9 ± 28.4 min; P = 0.72), and satiety rank was slightly higher for the Wolffia globosa shake compared with the yogurt shake (7.5 vs. 6.5; P = 0.035). CONCLUSIONS Wolffia globosa Mankai duckweed may serve as an emerging alternative plant protein source with potential beneficial postprandial glycemic effects.