This study aimed to understand Indonesian healthcare professionals’ (HCPs) perceptions and experiences regarding barriers to both HCP and community adherence to COVID-19 prevention guidelines in their social life. This methodologically qualitative study employed in-depth interviewing as its method for primary data collection. Twenty-three HCP participants were recruited using the snowball sampling technique. Data analysis was guided by the Five Steps of Qualitative Data Analysis introduced through Ritchie and Spencer’s Framework Analysis. The Theory of Planned Behaviour was used to guide study conceptualisation, data analysis and discussions of the findings. Results demonstrated that HCP adherence to COVID-19 prevention guidelines was influenced by subjective norms, such as social influence and disapproval towards preventive behaviours, and perceived behavioural control or external factors. Findings also demonstrated that HCPs perceived that community nonadherence to preventive guidelines was influenced by their behavioural intentions and attitudes, such as disbelief in COVID-19-related information provided by the government, distrust in HCPs, and belief in traditional ritual practices to ward off misfortune. Subjective norms, including negative social pressure and concerns of social rejection, and perceived behavioural control reflected in lack of personal protective equipment and poverty, were also barriers to community adherence. The findings indicate that policymakers in remote, multicultural locales in Indonesia such as East Nusa Tenggara (Nusa Tenggara Timur or NTT) must take into consideration that familial and traditional (social) ties and bonds override individual agency where personal action is strongly guided by long-held social norms. Thus, while agency-focused preventive policies which encourage individual actions (hand washing, mask wearing) are essential, in NTT they must be augmented by social change, advocating with trusted traditional (adat) and religious leaders to revise norms in the context of a highly transmissible pandemic virus. Future large-scale studies are recommended to explore the influence of socio-cultural barriers to HCP and community adherence to preventive guidelines, which can better inform health policy and practice.