Background: Antibiotic misuse and unsafe disposal harm the environment and human health and contribute to the global threat of antimicrobial resistance. Household storage of antibiotics for unsupervised use and careless disposal of medications is a common practice in China and most low- and middle-income countries. Currently, few interventions are available to address this challenge. Objective: This study assesses the feasibility and acceptability of an evidence-based, theory-informed, community-based take-back programme for disposing household’s expired, unwanted, or unused antibiotics in rural China. Methods: We adopted the RE-AIM framework and the community-based participatory research principles in the development, implementation, and evaluation of the intervention. The RE-AIM (reach, effectiveness, adoption, implementation, and maintenance) and Medical Research Council’s frameworks were employed in analysing and reporting evaluation results. A mixed-methods, controlled pre-and post-test design was used for (1) quantitative surveying of a representative community panel of 50 households, and (2) qualitative semi-structured stakeholders’ interviews to explore intervention and study design feasibility and acceptability at three phases: pre-intervention, intervention, and post-intervention. Quantitative and qualitative data from a similar village—serving as a control—were also collected. Results: All a priori feasibility objectives were met: Conversion to consent was 100.0% (100 screened, approached, recruited, and consented). All participants completed the pre-intervention assessment, and 44/50 households in the intervention village completed the post-intervention assessment. The programme, embedded in existing social and physical infrastructure for dissemination, directly reached over 68.2% (30/44) of its target audience. Stakeholders reported the intervention and study design as feasible and acceptable. Conclusions: This study illustrates the feasibility, acceptability, and potential efficacy of community-based antibiotic take-back programmes in China to encourage safe disposal and decrease the availability of expired, unwanted, or unused antibiotics in the household for unsupervised use.