Grandmothers often provide support for Mexican-origin mothers and young children. The factors influencing grandmother involvement, and the implications of this involvement for maternal well-being, particularly in the context of transborder family relationships, remain largely unexplored. This study considers the extent to which maternal, child, and intergenerational factors are linked with levels of grandmother involvement, and in turn grandmother involvement is associated with maternal psychological distress among an American community sample of 78 Mexican-origin families, for which over one third of grandmothers live in Mexico. Findings suggest that mother reported grandmother involvement is higher when children are temperamentally difficult, mothers perceive overall high-quality mother–grandmother relationships, and grandmothers live in the United States. Furthermore, extensive grandmother involvement when grandmothers live in Mexico is related to higher levels of psychological distress. These results highlight the importance of an intergenerational and transborder perspective on family relationships and well-being among Mexican-origin families.