Background <p>Unsafe disposal of unused and expired medications is an emerging environmental and public health concern, particularly in low– and middle–income countries. In Indonesia, evidence on medication disposal practices has largely been limited to small and localized studies, constraining policy development at the national level.</p> Objective <p>To assess public awareness and practices related to the disposal of unused and expired medications in Indonesia using nationally representative data, with secondary analyses stratified by residence and island to explore contextual differences.</p> Methods <p>A descriptive cross–sectional study was conducted using secondary data from the 2023 Indonesian Health Survey. Respondents aged ≥ 15 years from all 38 provinces were included (<i>n</i> = 616,110). Survey–weighted descriptive analyses were performed to estimate population–level awareness of damaged medicine indicators and reported disposal practices. Analyses were additionally stratified by area of residence and island to examine contextual differences in awareness and disposal behaviors.</p> Results <p>While most respondents (75.0%) recognized expiration as an indicator of damaged medicine, awareness of other critical indicators such as changes in color, odor, or packaging integrity was substantially lower. Unsafe disposal practices were widespread, with the vast majority discarding medicines in household trash (86.7%), and only a very small proportion (approximately less than 2%) returning medicines to appropriate collection systems. Stratified analyses revealed significant differences by residence and island, with rural populations more likely to engage in burning, burying, and storing medicines, while urban residents showed slightly higher awareness of non–expiration indicators. Substantial regional variation was also observed across island groups, with areas such as Maluku–Papua exhibiting higher reliance on informal disposal methods and slightly higher, yet still low, rates of medicine return.</p> Conclusions <p>Public awareness of medicine deterioration beyond expiration dates remains limited, and safe disposal practices are extremely rare across Indonesia. These findings highlight critical gaps in public knowledge and access to appropriate pharmaceutical waste management systems, underscoring the urgent need for nationwide education initiatives and the development of accessible, structured medicine take–back programs. Marked differences across residence and islands indicate that medication disposal behaviors are strongly shaped by contextual and structural factors, including disparities in waste management infrastructure, healthcare access, and availability of pharmaceutical services. These findings underscore the need for geographically tailored, context–specific interventions to effectively address gaps in safe medication disposal practices across Indonesia.</p>