Purpose: Glyphosate is a widely used non-selective herbicide. Previous studies have shown that glyphosate has genotoxicity, and that even low-doses of glyphosate can cause DNA damage. Melatonin is a hormone produced and secreted by the pineal gland that is known to be a potent anti-carcinogen, anti-oxidant, and genetic protector. This study was conducted to investigate the genoprotective effect of melatonin against glyphosate in human blood lymphocytes. Methods: Human peripheral blood was obtained from 15 young, healthy volunteers and cultured under four different toxicologic conditions. The four groups consisted of a control group, glyphosate only group (300 ng/mL), glyphosate with low level of melatonin group ($50{mu}M$), and glyphosate with high level of melatonin group ($200{mu}M$). The mean Sister Chromatid Exchange (SCE) frequency of each group was then analyzed. Results: Glyphosate exposed groups had a higher mean SCE frequency ($10.33{pm}2.50$) than the control group ($6.78{pm}2.31$, p<0.001). Interestingly, the group that received a low-level of melatonin had a lower mean SCE frequency ($8.67{pm}2.58$) than the glyphosate-only group, while the group that received a high level of melatonin had a much lower mean SCE frequency ($8.06{pm}2.50$) than the glyphosate-only group. There was statistical significance. Conclusion: Melatonin exerted a potent gene protective effect against the genotoxicity of glyphosate on human blood lymphocytes in a dose-dependent fashion.