Background <p>The aim of this study was to investigate the effects of maternal progesterone exposure on offspring neurodevelopmental outcomes, to ultimately provide insights for prevention strategies.</p> Methods <p>Using a retrospective observational approach, 256 children were recruited. Information on children’s general condition and mothers’ maternal history were collected via questionnaires and interviews, and neurodevelopment was assessed using Gesell developmental schedules. Multiple linear regression analysis explored the relationship between progesterone exposure and neurodevelopmental outcomes.</p> Results <p>Overall, 128 children were enrolled in the progesterone exposure (P) and non-exposure (C) groups, respectively. These groups showed no differences in the developmental quotient (DQ) scores of the gross motor, fine motor, and adaptive behavior domains; however, the P group showed significantly lower language and personal-social behavior DQ scores. After adjusting for offspring’s birth weight, length, and gestational age, maternal progesterone exposure and offspring’s language (<i>P</i> = 0.02), and personal-social behavior DQ scores showed negative correlations. After further adjustments for offspring sex, age, mode of birth, neonatal intracranial hemorrhage, neonatal asphyxia, maternal childbearing age, maternal educational level, folic acid administration, and assisted reproduction use, mother’s maternal gestational exposure to progesterone remained negatively associated with language and personal-social behavior.</p> Conclusions <p>Maternal progesterone exposure during pregnancy adversely affects offspring’s language and personal-social behavior development.</p>