Innovative interventions accessible to at-risk populations to prevent the intergenerational cycle of toxic stress are needed. This paper describes the iterative development of a community-based intervention, 2Gen Thrive, which was designed to prevent toxic stress and promote resilience by improving caregiver capacity to respond to children’s emotional, behavioral, and developmental needs. 2Gen Thrive leverages the collaboration between a Children’s Hospital and an Early Head Start/Head Start education center to help low-income, minority families thrive in the context of risk factors for toxic stress. In this paper, we focus on the process of developing, piloting, and refining our 2Gen Thrive preventive intervention research program, which has been developed following a community-based participatory research (CBPR) approach. The primary objective was to pilot test two prevention interventions we adapted for use in this target population: Classroom Theraplay, a classroom-wide intervention designed to prevent toxic stress among children exposed to adversity by fostering nurturing relationships with their teachers; and Dialectical Behavior Therapy Skills Training for Parents (DBT4P), a group intervention developed to bolster parental responsiveness by teaching Dialectical Behavioral Therapy (DBT) mindfulness and emotion regulation skills. We evaluated qualitative and process data as well as quantitative data from standardized instruments, including The Classroom Assessment Scoring System (CLASS), Patient Health Questionnaire (PHQ-9), Difficulties in Emotion Regulation Scale (DERS), and Parenting Stress Index (PSI/SF). Results demonstrate the feasibility, acceptability, and appropriateness of these preventive interventions delivered in the early education setting, and of conducting intervention research using a CBPR approach.