Abstract: Background and Objective: There are more than 7 million workers in the small and medium enterprises (SME) in Indonesia. The various occupational risks and environmental hazards threaten the health and well-being of these SME workers. It is important to promote occupational health and safety programs in order to improve quality of life (QOL). This study aimed to explore the socio-demographic profile and to examine the factors that impact the QOL among SME workers in Indonesia. Methodology: This study utilized a cross sectional study design. WHO quality of life (WHO-QOL) questionnaire was used to determine individuals perceptions of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards and concerns. Four domain scores include physical, psychological, environmental and social relationship. Sample for this study were 492 workers from 2 SME industries (food and textile). All of the industries were in registered in the Indonesia Ministry of Trade and Industry. Bivariate analysis was used by ordered logistic regression for quality of life in general with satisfaction of health as dependent variable and logistic regression for 4 domains as dependent variable. Results: The poor condition was found in social domain (36.58%, μ = 0.63, SD = 0.48), followed by psychological (32.32%, μ = 0.68, SD = 0.46), environmental (25.2%, μ = 0.75, SD = 0.43) and physical domain (17.47%, μ = 0.83, SD = 0.38). Quality of life among non-permanent employer was 0.5 times lower than permanent employees. Employees with higher educational level had better QOL (OR = 1.149 , CI = 1.063-1.242) in all domains. Employee with long duration of sleep had better QOL than those with short sleep duration. The SME workers who exercised regularly had 2 times better QOL (physical and social domain) and were more satisfied with their health than workers who did not exercise regularly. Conclusion: Socio-demographic factors influenced the quality of life among Indonesian workers, as well as job characteristics (work status, work shift and work area condition), individual characteristics (education level) and lifestyles (sleep duration and exercise habit).