The rising prevalence of noncommunicable diseases and mental health conditions has become a major challenge for public health and the long-term performance of Iran’s economy. These conditions can adversely affect national output and capital accumulation through premature mortality, disability, lower labor-force participation and productivity, and higher healthcare expenditures. This study estimates the macroeconomic burden of noncommunicable diseases and mental health conditions in Iran over the period 2020–2050. To this end, it employs a macroeconomic production framework augmented with human capital, in which diseases affect the economy through two main channels: a reduction in effective labor supply due to mortality and disability, and lower physical capital accumulation caused by treatment-related expenditures. The analysis draws on population projections, labor-force participation rates, capital stock, years of schooling, and disease-burden indicators based on DALYs and mortality. The cumulative disease burden over the study period was estimated at approximately 18.45 million DALYs, leading to a cumulative GDP loss of about Int$ 1,181 billion in 2024 PPP terms, equivalent to 2.33% of the country’s cumulative GDP. The largest shares of this loss are attributable to cardiovascular diseases, cancers, and diabetes and kidney diseases. Sensitivity analysis further indicates that the main conclusion regarding the substantial economic burden of these conditions remains broadly robust. These findings highlight the importance of strengthening prevention policies, early diagnosis, chronic disease management, and mental health services in Iran.