Background Antimicrobial resistance (AMR) is a growing public health threat, particularly in low- and middle-income countries (LMICs) where antibiotic misuse is common and awareness is limited. In Cambodia, misconceptions about antibiotics, such as their use for viral infections and common ailments, are widespread. Culturally relevant strategies are needed to communicate complex health messages to diverse audiences. This study aims to explore the impact of a co-designed, circus-based engagement project on community understanding and perceptions of AMR and antibiotics. Methods A qualitative case study design was employed. From May 20 to June 25, 2025, data were collected through 15 Semi-Structured Interviews (SSI) and three Focus Group Discussions (FGD) following performances in Battambang and Siem Reap provinces. Participants represented varied backgrounds and ages (16-60 years). The SSIs and FGDs, conducted in Khmer and translated into English, were complemented by field observations from live performances. All transcripts underwent thematic analysis, and findings are presented based on the research question. Results Four key themes were identified: (1) Baseline knowledge and misconceptions ‒ antibiotics were often seen as general-purpose medicines, (2) Community medicine use ‒ treatment-seeking relied heavily on informal sellers, peer recommendations, and often entailed incomplete courses, (3) Audience interpretation of the performances ‒ humour and familiar scenarios supported message recall, though some confusion remained, (4) Key takeaways and intended change ‒ many participants reported plans to seek medical advice from appropriate health services before taking antibiotics and to share correct information with others. Conclusions Circus-based engagement was received as a creative and culturally resonant form of health communication that could translate complex biomedical concepts into accessible, and memorable narratives. In Southeast Asia and other LMIC settings with high AMR burdens, such co-designed approaches to knowledge translation could complement conventional education strategies and bridge the gap between scientific knowledge and everyday health practices.