Pregnancy can affect the absorption, distribution, metabolism, and excretion of several drugs due to pregnancy-induced physiological changes. Risperidone, a second-generation antipsychotic, is prescribed to pregnant women when the benefits outweigh the risks to the fetus. Serum concentrations of risperidone and its active metabolite paliperidone in a pregnant woman as well as her newborn were measured, and physiologically-based pharmacokinetic (PBPK) models of both drugs were developed. The effects of pregnancy on pharmacokinetic parameters of both drugs were quantitively assessed by the developed PBPK model. As a result, serum concentrations of risperidone and paliperidone decrease in the pregnant status and abruptly recover to the non-pregnant level after delivery mainly due to cytochrome P450 (CYP) 2D6 activity changes, and therefore, close and careful monitoring of clinical symptoms should be considered during pregnancy and after delivery. In the 10 different models for estimating the renal function of children, the Flanders metadata equation showed the lowest absolute bias and the greatest precision in predicting paliperidone serum concentration in the neonate. PBPK model-informed approach could help with the precision dosing in special populations, such as pregnant women and neonates.