Abstract Objectives Multiple studies have examined the effects of fresh watermelon, watermelon juice, or watermelon powder on satiety and skin health; however, few studies have addressed the effects of blenderized (flesh, rind, and seeds) watermelon juice. The objective of this study was to determine the effects of blenderized watermelon juice consumption on satiety, postprandial glucose, insulin response, and topical application on skin health in healthy adults. Methods In a crossover design, subjects (N = 20, 16 females, 4 males, age 22.8 ± 2.5 y, BMI 22.6 ± 2.80 kg/m2) consumed 8 fl oz of either blenderized watermelon juice or isocaloric sugar water. After an overnight fast, blood glucose and insulin levels were measured at baseline, and at 30 and 60 minutes after drink consumption. Measurements for satiety using a visual analogue scale and skin health using a moisture content test were conducted at baseline, right after, 15, 30, 45, and 60 minutes after consumption and topical application of the juices. Results Both blenderized watermelon and sugar water significantly increased satiety (P < 0.001) but there was no difference between the two trials. Postprandial glucose (P = 0.030) and insulin levels (P = 0.007) significantly increased after the consumption of sugar water compared to blenderized watermelon juice. Topical application of blenderized watermelon juice on the skin significantly increased skin moisture level (P = 0.012) compared to the sugar water application. Conclusions The consumption of blenderized watermelon promoted satiety, stabilized postprandial glucose and insulin levels, and improved skin health. These results suggest that blenderized watermelon juice may be beneficial for those who are overweight or obese and/or are at risk of developing diabetes. Further watermelon studies are warranted to examine long-term effects. Funding Sources National Watermelon Promotion Board (NWPB 19-20).