This study was performed to investigate the effects of bitter melon extract (BME) on glucose metabolism, insulin resistance, and various metabolic parameters of participants with prediabetes. A 12-week randomized placebo-controlled clinical study was conducted with prediabetic patients. A total of 76 participants were randomly assigned to initiate the study. In the final analysis, 33 and 32 subjects were included in the BME and placebo groups, respectively. Results showed that 75 g oral glucose tolerance test (OGTT) blood glucose level decreased in BME group after 12 weeks. The glucose level after 30 min of glucose ingestion decreased significantly. The glucagon level in the BME group after 12 weeks significantly decreased 120 min after 75 g OGTT. These results suggested that bitter melon exhibits glucose-lowering effects through suppression of glucagon levels in people with prediabetes.