Purpose: The aim of this study was to identify the mediating effects of perceived stigma and family strength on the relationship between family stress and adaptation in family members of patients with mental illness. Methods: Participants were 189 primary family caregivers of persons with mental illness in G city, C, G, and J provinces. Data were collected from May to June 2018 using the FILE (Family Inventory of Life Events and Changes), K-ISMI (Korean Version of Internalized Stigma of Mental Illness Scale), FAS III (Family Adaptability Scale III), and KFSS-II (Korea Family Strengths Scale). Collected data were analyzed with t-tests, one-way ANOVAs with Scheffe' test, Pearson's correlation coefficients, and PROCESS macro mediation analysis. Mediators were tested by calculating bias-corrected 95% confidence intervals using bootstrapping with 5,000 resampling. Results: Family stress was directly associated with family adaptation. Family strengths had a partially mediating effect on the relationship between family stress and adaptation, but perceived stigma did not. Conclusion: Based on our study findings, developing a nursing intervention program focused on improving family strengths might be necessary to facilitate family members' successful adaptation to persons with mental illness.