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Aim: To analyze the burden of disease due to mental and substance use disorders in Peru from 1990 to 2015 obtained from the Global Burden of Disease study 2015. Subject and methods: A descriptive study quantifying the burden of disease using disability-adjusted life years (DALYs), calculated by taking the sum of years of life lost (YLLs) and years lost due to disability (YLDs). We adjusted for comorbidities and estimates are presented with 95% uncertainty intervals. Findings specifically pertaining to Peru including DALYs, YLLs, and YLDs by year, sex, age, and type of disorder for the years 1990 and 2015 are presented. Results: In 2015, mental and substance use disorders ranked as the leading cause group of DALYs in Peru comprising 11.71%, which is twice as much as that in 1990 (5.28% of DALYs). The five leading causes of health loss included: depressive disorders, anxiety disorders, substance use disorders, schizophrenia, and bipolar disorder. Women represented 50.98% of the total DALYs. The highest DALYs were found in 10–54-year-olds and was greater among 20–29-year-olds. Among total YLLs, psychiatric diseases represented only 0.71%, with drug use disorders listed as the highest cause in 2015, as opposed to alcohol use disorders in 1990. Of the total YLDs, psychiatric disorders represented 23.41%, with depressive and anxiety disorders being the leading causes. Conclusions: Mental and substance use disorders represent an important cause of disability in 2015 for Peru. Depressive and anxiety disorders were found to be the most prominent cause of disease burden across all age groups, particularly among females. Peru must make the prevention and treatment of mental disorders a public health priority.