Introduction: In preeclampsia (PE), impaired trophoblast proliferation and differentiation are thought to cause abnormal placentation and subsequent clinical manifestations of the disease—i.e., hypertension, proteinuria, and end-organ damage. Insulin-like growth factor 1 (IGF-1) influences trophoblast cell function, however the mechanisms of IGF-1’s action on trophoblasts is not well understood. Inhibitor of DNA binding protein 2 (ID2) is involved in trophoblast differentiation and implicated in many processes disrupted in PE including placental development, vascular differentiation, and angiogenesis. We hypothesized that IGF-1 regulates trophoblast proliferation and differentiation via ID2. Methods: Immortalized human first trimester trophoblast cells (HTR-8/SVneo) were treated with IGF-1 for 24 hours after serum starvation. ID2 mRNA and protein were measured, as well as trophoblast cell viability, proliferation, tube formation and migration. Results: IGF-1 decreased ID2 expression in a dose-dependent manner. IGF-1 decreased trophoblast proliferation but increased cell viability, differentiation, and migration. ID2 overexpression mitigated the effects of IGF-1 on trophoblast cells. Discussion: These data suggest IGF-1 could regulate trophoblast proliferation and differentiation through ID2. Dysregulation of ID2-mediated IGF-1 signaling in trophoblast cells could be involved in the pathogenesis of pregnancy disorders like uterine growth restriction and PE.