Cucumis melo var. flexuosus (C. melo var. flexuosus) is one of the ancient horticultural crops in many parts of the world. However, there has been no study reported its effects on diseases. Therefore, the aim of present study was to investigate antioxidant and antidiabetic activities of C. melo var. flexuosus leaf. First, the antioxidant activity of snake melon leaf extract was determined. Then the biochemical parameters for diabetic rats treated with snake melon (30, 60 and 120 mg/kg b.w) were investigated. The leaf extract showed a high antioxidant activity. Further, diabetic rats treated with snake melon leaf extract showed a significant decrease in the levels of blood glucose, total cholesterol, triglycerides and low-density lipoprotein cholesterol, lactate dehydrogenase, liver enzymes, and malondialdehyde and a significant increase in insulin, body weight, high-density lipoprotein cholesterol, total protein, catalase and superoxide dismutase levels. This study demonstrated the antioxidant and antidiabetic activities of leaf extract of snake melon.