Background A balanced maternal diet during pregnancy is essential for child growth, development, and lifelong health. Micronutrients obtained from mother’s diet are important for several processes in pregnancy including placentation and antioxidant defence system. Too much oxidative stress can adversely affect placental development and functions. Poor placentation and oxidative stress are associated with pregnancy adverse outcomes such as preeclampsia and preterm birth. Epidemiological studies have shown that lower maternal levels of selenium and iodine are associated with a higher incidence of a complicated pregnancy. These two essential micronutrients may be involved in neutralizing oxidative stress; thus higher placentation quality and healthy pregnancy outcomes. Aim To determine how selenium, iodine, and their combination may impact oxidative stress in HTR-8/SVneo trophoblast cells. Method HTR8 cells were supplemented with mineral or organic selenium compounds, iodine, or their combination for 24 hours. Cells were then treated with menadione or hydrogen peroxide (H2O2) for 24 hours to simulate endogenous or exogenous oxidative stress, respectively. Cell viability and also lipid peroxidation as the biomarker of oxidative stress were assessed at the end of treatments. Results Both menadione and H2O2 decreased cell viability and increased lipid peroxidation, significantly. Supplementation with selenomethionine or sodium selenite was associated with higher cell viability (P<0.05). Lipid peroxidation in cells-supplemented with selenium or iodine separately or together was significantly lower in comparison to no supplemented cells (P<0.05). Conclusion Selenium and iodine may protect placental cells against oxidative stress which is important for a healthy pregnancy. Currently we are expanding this research by performing similar experiments on first trimester placental tissue.