Background <p>Antimicrobial resistance (AMR) poses a critical global health challenge, exacerbated by the misuse of antibiotics. The COVID-19 pandemic has heightened this issue, particularly in low- and middle-income countries, where self-medication with antibiotics is common. This study aimed to explore the prevalence, socio-demographic factors, and behavioral drivers of non-prescription antibiotic use in Kazakhstan during the COVID-19 pandemic.</p> Methods <p>A cross-sectional online survey was conducted among adults in Kazakhstan using a snowball sampling technique. The questionnaire, adapted from the WHO Europe behavioral insights tool, assessed socio-demographics, COVID-19 perceptions, preventive behaviors, trust in information sources, and beliefs in conspiracy theories.</p> Results <p>The study included participants aged 18–74 years, with non-prescription antibiotic use more prevalent among rural residents and caregivers of children under 18 years (<i>p</i> &lt; 0.001). Individuals perceiving a high probability and severity of COVID-19 were more likely to self-medicate with antibiotics (<i>p</i> &lt; 0.001). Interestingly, low trust in healthcare professionals was significantly associated with antibiotic misuse (<i>p</i> &lt; 0.001). Despite widespread adherence to preventive measures, individuals who self-medicated exhibited higher compliance rates with handwashing, mask-wearing, and surface disinfection (<i>p</i> &lt; 0.05). Additionally, participants who expressed greater worry about COVID-19-related issues, including losing loved ones or economic instability, were less likely to misuse antibiotics. Belief in conspiracy theories was relatively uncommon but associated with reduced antibiotic misuse in certain scenarios.</p> Conclusions <p>The findings underscore the need for targeted public health strategies to address disparities in healthcare access, build trust in medical professionals, and enhance antibiotic stewardship efforts to mitigate AMR risks in Kazakhstan.</p>