Plant development depends on the environmental conditions, and the accumulation of heavy metals in plant tissues causes various molecular and biochemical changes in plant life cycles. Plants have developed a number of detoxification mechanisms to tolerate oxidative damages in the unsuitable environments. GR and GST involved with glutathione are the key antioxidant defense enzymes in response to heavy metals stress. In the present study, mRNA expressions and activities of GR and GST enzymes are investigated in the leaves of tomato (Lycopersicon esculentum Mill.) increasing doses of Cd, Cu, and Pb. The transcriptional expression of GR and GST was analyzed by real-time quantitative PCR. GR and GST genes are induced compared to control in leaves of tomato by the application of heavy metals. The expression of GR usually significantly increased except for 10 ppm of Pb which there was no significant change in the low dose. The GST transcript significantly raised in all treatment of heavy metals. The highest expression of GR and GST was observed in the application of 20 and 50 ppm of Pb, respectively. The enzyme activities of GR and GST significantly increased by the application of Cd, Cu, and Pb, but GR activity remained constant at 50 ppm of Cu compared to control in leaves of tomato. The results presented in this study indicate that the transcript expressions show a correlation with enzymes activities with small differences because post-transcriptional factors might affect the enzymes activities.