BACKGROUND: Chronic diseases are known to detrimentally impact an individual's quality of life (QOL) and well-being. Therefore, this study aims to evaluate the QOL and overall well-being among both healthy individuals and those with diverse primary diagnoses. METHODS: This is a cross-sectional study and data collection took place from May 2022 to May 2023. Information regarding healthy participants was gathered from healthcare workers without any comorbidities. Data for non-healthy participants were collected from individuals diagnosed with various conditions across four specialist clinics: nephrology, oncology, psychiatry, and cardiology. All participants completed the Significant Quality of Life Measures (SigQOLM), a comprehensive assessment tool consisting of 69 items that evaluate 18 domains of QOL and well-being. RESULTS: The study included a total of 452 participants, with 284 (62.8%) classified as healthy. Among the non-healthy participants, 41 (9.1%) had end-stage renal diseases (ESRD), 48 (10.6%) were diagnosed with cancer, 40 (8.8%) had depressive disorder, and the remaining had heart disease (8.6%). Statistical analysis revealed significant differences (p <
0.001) between healthy and non-healthy participants in both overall SigQOLM scores and across all 18 domains of SigQOLM. CONCLUSION: Generally, healthy participants also experienced excellent QOL and well-being. However, disparities in both QOL and overall well-being were evident among patients with various diagnoses. These findings provide valuable insights for medical practitioners and policy makers by enabling them to tailor interventions to enhance the QOL and well-being of their patients.