Little is known about internalized stigma of mental illness in India. A reason for this could be the lack of valid assessment instruments adapted for the diverse cultures and languages of the country. One of the most widely used and accepted questionnaires to assess internalized stigma is the 29-item Internalized Stigma of Mental Illness (ISMI) scale. The aim of the present study was to translate and adapt the ISMI to the Malayalam-speaking population of Kerala, India and to assess its content and factorial validity. The content validity of the Malayalam-language ISMI was studied through interviews with 7 experts on stigma in India. Factorial validity was examined by means of a confirmatory factor analysis (CFA) based on a cross-sectional survey among 290 patients with mental illness attending follow-up outpatient and primary care clinics in Kerala, India. The expert panel concluded that the items of the translated questionnaire adequately represent internalized stigma in the Malayalam-speaking population of Kerala. The theorized factor structure of the ISMI consisting of five factors showed a suboptimal model fit (WRMR = 0.940; TLI = 0.971, CFI = 0.948; RMSEA = 0.059) which improved considerably after removal of the stigma resistance factor and three items with poor factor loadings (WRMR = 0.819; TLI = 0.982, CFI = 0.966; RMSEA = 0.051). Although our study identifies some sources of model ill-fit, it shows that a reduced version of the Malayalam-language ISMI can be a valuable tool for the study of internalized stigma in this cultural setting.