This study conducted an online survey using a structured questionnaire on 1 January to 29 February 2024, targeting 1,376 residents of Anhui Province to collect information on demographic characteristics, knowledge literacy regarding antimicrobial use, interpersonal networks, health service environment, and whether they had taken antimicrobials. Chi-square tests and multivariate logistic regression analysis were used to explore the factors influencing residents' irregular use of antimicrobials. The results showed that in the past three months, 548 respondents had taken antimicrobials. Among them, 56.39% exhibited three or more irregular medication behaviors. Multivariate logistic regression analysis found that living in urban areas, poor knowledge literacy regarding antimicrobial use, low perceived benefits, low perceived barriers, and limited understanding of drug policies were risk factors for irregular drug use among residents; while being less influenced by interpersonal networks was a protective factor. Irregular use of antimicrobials is relatively common among residents in Anhui Province. It is recommended that relevant departments formulate multi-level health education strategies around residents' health ecological environment to comprehensively improve rational drug use behaviors.