The purpose of this mixed-methods study was to develop and evaluate a home-based palliative care model that included specific meditation healing exercises (SKT6) among end-stage renal disease (ESRD) patients in Thailand. In total, 74 persons participated in the quantitative portion, and 120 contributed to the qualitative design. Qualitative data collected included situation analysis and focus group interviews. Quantitative data collected included demographic data, uncertainty in illness, and quality of life (QoL) for dialysis patients, care satisfaction, the Edmonton physical symptom assessment scale, and blood chemistry before and after the quasi-experimental SKT6 intervention. The situational analysis identified home-based palliative care problems in setting, barriers, and facilitators in the community, including a strengths, weaknesses, opportunities, and threats (SWOT) analysis of home-based palliative care. The qualitative interviews and survey results revealed that people living with ESRD and their families experienced great suffering, as well as uncertainty associated with the illness and lack of management of palliative care in the community. From the beginning to the end of the study, the range of the Mishel uncertainty-in-illness score increased, from 29 to 86. The physical assessment in the Edmonton Symptom Assessment Scale instrument results ranged from 0 to 61 (mean, 21.59 [SD, 16.68]). After practicing SKT6, the QoL among dialysis patients improved, from 6.71 to 27.97 (mean, 19.38 [SD, 4.24]). People living with ESRD were trained to practice SKT6 meditation exercises. The survey was completed prior to meditation healing exercises and after their implementation. After this intervention, people living with ESRD had higher scores for satisfaction with the home-based palliative care program. Satisfaction levels increased, from 38.05 to 62.93; well-being increased, from 5.60 to 7.85; psychological and spiritual well-being increased, from 21.17 to 28.54; and total QoL scores increased, from 18.44 to 23.65. The SKT6 meditation healing exercises affected the QoL, satisfaction, and uncertainty in life with the illness significantly.