Substance use during pregnancy and the postpartum period may have significant implications for both mother and the developing child. However, the neurobiological basis of the impact of substance use on parenting is less well understood. Here, we examined the impact of maternal substance use on cortical gray matter (GM) and white matter (WM) volumes and whether this was associated with individual differences in motivational systems of behavioral activation and inhibition. Mothers were included in the substance-using group if any addictive substance was used during pregnancy and/or in the immediate postpartum period (within 3 months of delivery). GM volume was reduced in substance-using mothers compared to non-substance-using mothers, particularly in frontal brain regions. In substance-using mothers, we also found that frontal GM was negatively correlated with levels of behavioral activation (i.e., the motivation to approach rewarding stimuli). This effect was absent in non-substance-using mothers. Taken together, these findings indicate a reduction in GM volume is associated with substance use and that frontal GM volumetric differences may be related to approach motivation in substance-using mothers.