Display omitted •Perchlorate exposure caused significant histopathological changes in human placenta.•A significant increase in ROS generation and caspase-3 expression were found.•15 μg/L perchlorate significantly reduced placental CYP 19 activity.•15 μg/L perchlorate significantly reduced placental cellular viability.•Perchlorate concentration (5 μg/L) did not affect placental cellular viability. Perchlorate is a strong oxidizing agent and has many adverse health effects. This study investigated the potential oxidative, apoptotic, and endocrinal toxic effects of perchlorate in human placenta-derived mesenchymal stem cells (HP-MSCs). HP-MSCs were treated with two doses of perchlorate (5 and 15 μg/L) for three days. The perchlorate’s effects were detected by histopathological examination, aromatase/CYP19 A1 activity, reactive oxygen species production (ROS), and Caspase-3 expression. The highest perchlorate concentration (15 μg/L) caused significant placental histopathological changes. The placental cell viability was significantly affected by a significant increase in ROS generation; caspase-3 expression, and a significant reduction of CYP 19 activity. Despite the slight induction effect of the lowest perchlorate concentration (5 μg/L) on caspase 3 expression, CYP 19 activity, and ROS generation, it did not affect placental cellular viability. This study suggested that perchlorate could modulate aromatase activity and placental cytotoxicity. The continuous monitoring of the actual perchlorate exposure is needed and could be cost-effective.