Momordica charantia, commonly known as bitter gourd, is a therapeutic plant popularly known for its antidiabetic potential in folklore medicine. This study investigated the effect of aqueous leaf extract of M. charantia (AMC) on survival rate, locomotive behaviour and antioxidant response in Drosophila melanogaster.  Adult flies were fed with different concentrations of AMC (0-100 mg/mL) for 12 days, and their locomotive behaviour and whole-body antioxidant status were assessed at 0, 2, 4 and 8 mg/mL of AMC.  Results showed a significant decrease (p < 0.05) in the survival rate and locomotive behaviour of flies at 8, 16 and 50 mg/mL of AMC compared to the control. There was no significant difference in malondialdehyde content, GSH level and SOD activity of flies exposed to 2, 4, and 8 mg/mL of AMC compared to the control group. Glutathione-s-transferase activity at 8 mg/mL of AMC increased significantly (p < 0.05) when compared to the control group.  Acetylcholinesterase activity also increased in a dose-dependent manner with a significant increase at 4 and 8 mg/mL of AMC. The evidence from this study suggests that low to moderate doses of aqueous extract of Momordica charantia slightly improved survival rate of flies. It also increased the activities of acetylcholinesterase and antioxidant enzymes.