Overuse and misuse of antibiotics are associated with increased antibiotic resistance globally, including in Thailand. Community pharmacies in Thailand can supply antibiotics directly to patients without a prescription. Inappropriate supply of antibiotics from Thai community pharmacies to the public for common, self-limiting diseases, such as, upper respiratory infections, acute diarrhoea and wounds has been reported. This study aimed to explore barriers that might make it difficult to comply with the rational use of antibiotics in community pharmacies in Thailand. A purposive sample of community pharmacists in six provinces in Thailand were invited to participate. Individual semi-structured interviews were conducted in Thai, transcribed and analysed inductively using thematic analysis. Ethics approval was obtained from Cardiff and Ubon Ratchathani Universities. Twenty-three community pharmacists were recruited (urban/rural, chain/independent, male/female and with a range of experience). In terms of barriers to comply with antibiotic treatment guidelines three themes were identified: (1) barriers related to patients: patients’ lack of knowledge about indications for antibiotics, patients’ perceptions regarding benefits, or otherwise, of antibiotics, advice from those other than healthcare professionals, (2) barriers related to community pharmacists: conflict of interest between pharmacy profession and business, lack of updated knowledge relating to antibiotic use, and pharmacists’ views toward antibiotic resistance and (3) regulatory factors (Thai pharmacy regulator and government): need for strengthened enforcement of laws and regulations related to antibiotic supply. Pharmacists reported several barriers to being able to comply with the rational use of antibiotics. Community pharmacists perceived a lack of knowledge by patients and the business model of pharmacy to be important barriers. Further research is required to determine if these views are prevalent across larger numbers of community pharmacists, and other stakeholders, across Thailand so that improved appropriate supply of antibiotics from community pharmacies in Thailand can be facilitated.