BACKGROUND Antimicrobial resistance (AMR) has emerged as one of the most serious threats to global public health. The proliferation of social media platforms as digital channels for health information has facilitated the dissemination of personal experiences with antibiotic use, but some of this information may be misleading. Such misleading information may encourage the inappropriate use of antibiotics, thereby accelerating AMR. Despite growing concerns, there remains a significant gap in the literature regarding both the quality of information in these posts and the specific features that drive their popularity. OBJECTIVE Taking sore throat as a focal case, this study aims to achieve two primary objectives: (1) to systematically evaluate the informational quality of social media posts that share personal experiences with antibiotic treatment and (2) to quantitatively identify specific features associated with higher levels of audience engagement. METHODS The data were collected from a leading social media platform, Xiaohongshu, to conduct this study. Two clinical pharmacists assessed the appropriateness of the medication-related practices described in the posts and coded the relevant features, which are identified according to the Elaboration Likelihood Model (ELM) and the Health Belief Model (HBM). Negative binomial regression was employed to examine the effects of these features on user engagement, as measured by the number of likes and collections. RESULTS Among the 1061 posts analyzed, the overall quality of the antibiotic-related posts was worrisome. As many as 31.39% of the posts involved antibiotic use without clinical indication, and many displayed issues related to suboptimal drug selection and inappropriate dosing regimens. In examining features associated with post popularity, this study found that the presence of treatment information in post title (likes: incidence rate ratio (IRR)=1.65, P<.001; collections: IRR=1.92, P<.001), the use of a well-designed cover image (likes: IRR=1.43, P=.002; collections: IRR=1.67, P<.001), and the inclusion of recovery outcome (likes: IRR=2.02, P<.001; collections: IRR=2.28, P<.001), detailed description (likes: IRR=2.08, P<.001; collections: IRR=2.14, P<.001), and advice (likes: IRR=1.78, P<.001; collections: IRR=2.14, P<.001) in the content were all significantly associated with increased user engagement. In addition, the imperative language and linguistic intensifier in post titles had different effects during the COVID-19 pandemic's peak and stable phases. CONCLUSIONS The findings of this study indicate that the quality of personal antibiotic treatment experiences shared on social media is concerning. Furthermore, the study identified several post features that are associated with increased popularity in this context. The findings provide valuable insights for health authorities in developing more effective health promotion strategies.