High rates of type 2 diabetes (T2DM) and depression exist in rural Appalachia with limited access to psychotherapeutic treatment. No manualized cognitive behavioral therapy (CBT) treatment materials exist that are culturally tailored for individuals in this region with T2DM. We describe the development of the Program ACTIVE CBT intervention for use with adults with T2DM and depression by mental health providers in rural Appalachia. Qualitative and quantitative methods were used to test the feasibility and acceptability of Program ACTIVE. Intervention materials were rated at the 6th-7th grade reading level. Key informant interviews evaluated materials as culturally sensitive and accessible. Participants indicated high levels of satisfaction with therapy (94%), support from their therapist (86%), and usefulness of therapy and depression improvement (80.3%). Program ACTIVE was found to be a feasible and acceptable culturally tailored manualized CBT treatment for adults with T2DM and depression living in rural Appalachia. Implementation of these materials on a regional scale needs to be assessed.