Objectives The study aimed to develop a regional version of the Malocclusion Impact Questionnaire (MIQ-Malayalam) for the Malayalam-speaking Indian population. Methods The English version of MIQ was translated into Malayalam through a rigorous translation process, followed by cross-cultural adaptation. Young people aged below 18 years who were just about to start orthodontic treatment were invited to complete the Malayalam version of MIQ along with the available native version of the Psychosocial Impact of Dental Aesthetics Questionnaire (PIDAQ). The MIQ-Malayalam was readministered after 14 days to assess test-retest reliability. Treatment need was assessed normatively using the Dental Health Component of the Index of Orthodontic Treatment Need (IOTN-DHC) and subjectively using Aesthetic Component of the Index of Orthodontic Treatment Need (IOTN-AC). Results A total of 210 subjects completed the questionnaires (males = 47.2%; females = 52.8%; age = 12-17 years, mean = 15 years and 3 months; standard deviation = 1.9) and 50 completed repeat questionnaires. Internal consistency and test-retest reliability were high (Cronbach’s alpha = 0.952; Intra-class Correlation Coefficient = 0.93). Exploratory factor analysis derived 4 factors with exclusion of 1 item. There were significant differences ( P < .05) in MIQ scores between IOTN-DHC subgroups, ensuring discriminant validity. There was a high correlation between total MIQ and total PIDAQ scores (rho = 0.884), while low between total MIQ and IOTN-AC scores (rho = 0.203). Conclusion The Malayalam version of MIQ was found to be valid and reliable and can serve as a useful condition-specific measure of oral health-related quality of life.