Standardized Western resilience scales may not adequately capture culturally grounded protective factors in global contexts. This mixed-methods study developed a culturally informed Kenya Resiliency Index (KRI) based on ethnographic interviews identifying locally relevant constructs such as spiritual support, community connectedness, and social relationships. Among 206 Kenyan adults aged 35–81, linear regression models demonstrated that the KRI showed significant direct protective effects against depressive symptoms and significantly moderated the relationship between life stress and depression. In contrast, the commonly used Connor-Davidson Resilience Scale (CDRS-10) showed neither effect. These findings illustrate the importance of culturally adapted psychological measures and show that resilience exerts both direct and buffering effects on mental health outcomes. Future work should validate the KRI across additional Kenyan populations and examine applicability in caregiver and clinical settings.