Background: Globally, chronic diseases are on the rise. These diseases tend to require lifelong therapy and frequent medical surveillance. Advanced knowledge, technology and treatment approaches have resulted in longer survival rates for patients suffering from acute and chronic diseases. However, the symptoms for such diseases persist and affect the individual's whole life and normal functioning. Symptoms and quality of life among patients with chronic diseases are not adequately explored in Oman and Arab countries despite the increasing number of people living with chronic diseases. Aim: The main study purpose is to assess symptoms prevalence, severity, distress, quality of life, and predictors of quality of life among patients with selected nonmalignant chronic diseases in Oman. Chronic diseases include chronic obstructive pulmonary disease (COPD), end-stage renal disease (ESRD) and chronic heart failure (CHF). Method: A quantitative descriptive cross-sectional design was used and a convenience sample of 340 adult patients was recruited from two hospitals and one dialysis centre in the Sultanate of Oman, Muscat Governate. The Memorial Symptoms Assessment Scale (MSAS) was used to assess symptoms prevalence, severity, frequency, and distress while the 36-Item Short Form Health Survey (SF-36) was used to assess quality of life. In addition, the Karnofsky Performance Status Scale (KPSS) was utilized to estimate participants' functional status. Descriptive statistics were applied to analyse symptoms profile and quality of life domains. Moreover, multiple linear regression was used to predict the mean score of quality of life mental and physical domains. Results: Patients with selected chronic diseases (COPD, ESRD, CHF) experienced an average of 7.4 (SD = 4.4) symptoms at the same time. The highly prevalent symptoms were lack of energy Symptoms and Quality of Life (60.9%), pain (57.4%), numbness (53.2%), difficulty sleeping (49.4%) and shortness of breath (45.9%). The most severe symptoms were shortness of breath (53.2%), problems with urination (51.9%), constipation (50.8%), difficulty sleeping (49.7%) and pain (46.2%). The symptom "problems with sexual interests or activity" was found to be the most frequently occurring and highly distressing symptom out of all the reported symptoms. Quality of life among patients with selected chronic diseases was greatly affected. The mean score of the quality of life for the physical health domain was 51.1 (SD = 24.5) and the mean score for the mental health domain was 74 (SD = 16.5). Using multiple linear regression, being married and having high score of the Karnofsky Performance Status Scale (KPSS) predicted higher scores on the mental and physical domains of quality of life. In addition, a lower mental health domain score was found to be predicted by having a higher number of total symptoms and having COPD, while a lower physical health domain score was found to be predicted by older age, a higher total symptoms number and higher distress level. Conclusion: Patients with chronic nonmalignant diseases experience various symptoms that can be severe, distressing and impact their quality of life. Therefore, understanding symptoms experience, quality of life and its predictors among patients with chronic diseases is essential in planning and implementing management plans. It is also critical when implementing interventions to improve quality of life. In Oman, the knowledge generated from this study can guide the clinical management and palliative care services for patients with chronic diseases. Further, future studies are advised to explore symptoms cluster and consider the stage and severity of the chronic diseases.