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Rural, low-income mothers face higher risk for poor health literacy and depression compared to the general population. While the association between health literacy and depression has been documented, the underlying mechanism of this relationship is not clear. Focusing on 304 low-income mothers in rural communities, this study examined the role of family context—alliance between parents and prevalence of healthful eating and physical activity in the home—in this association. Hierarchical regression followed by mediation analyses were conducted on mother’s depressive symptoms controlling for mothers’ demographic characteristics and access to healthcare. Lower health literacy was significantly associated with higher risk for depressive symptoms with parenting alliance partially mediating the relationship between health literacy and depressive symptoms. The finding suggests that alliance between parents is a critical aspect of mothers’ social support system that may offset the negative impacts of poor health literacy on their mental health. Possible discrepancies between mothers’ knowledge and their actual behaviors as well as mothers’ awareness of low health literacy and their sense of need for assistance are presented along with implications for healthcare professionals and social workers.