ObjectivesSelf-medication with antibiotics (SMA) contributes significantly to the emergence of antimicrobial resistance (AMR), especially in low-income countries including Bangladesh. This study aimed to generate evidence on the self-reported prevalence of antibiotic self-medication and its determinants among indigenous people residing in Bangladesh’s Chittagong Hill Tracts (CHT) districts.DesignThis study used a cross-sectional design with data collected through a survey using a semi-structured questionnaire.SettingThis study was conducted from late January to early July 2021; among different indigenous group populations aged 18 years or more olders residing in the three districts of CHT.ParticipantsA total of 1336 indigenous people residing in Bangladesh’s CHT districts were included.Primary outcome and explanatory variablesThe primary outcome measure was SMA while explanatory variables were socio-demographic characteristics, health status of participants, and knowledge of antibiotics usage and its side effects.ResultsAmong the study participants, more males (60.54%) than females (51.57%) reported using antibiotics. The SMA rate was high among individuals with education levels below secondary (over 50%) and those in the low-income group (55.19%). The most common diseases reported were cough, cold and fever, with azithromycin being the most frequently used antibiotic. Levels of education, family income, having a chronic illness and place of residence were found to be the significant predictors of having good knowledge of antibiotic use as found in the ordered logit model. Findings from a logistic regression model revealed that men had 1.6 times higher odds (adjusted OR (AOR) 1.57; 95% CI 1.12 to 2.19) of SMA than women. Participants with ≥US$893 per month family income had lowest odds (AOR 0.14; 95% CI 0.03 to 0.64) of SMA than those who earned <US$417. Participants living in Rangamati districts had a lower risk of SMA (…) than those in Bandarban district. rate of SMA (AOR 0.52; 95% CI 0.30 to 0.90) than those in Bandarban district.ConclusionMale gender, family income, place of residence and knowledge of antibiotics were the significant predictors of antibiotic self-medication. Hence, it is important to streamline awareness-raising campaigns at the community level to mitigate the practice of SMA in indigenous people and ultimately address the devastating effects of Antimicrobial resistance (AMR) in Bangladesh.