BACKGROUND: The objective of this study was to investigate the impact of microRNA-205-5p (miR-205-5p) on clinical outcomes in patients with polycystic ovary syndrome (PCOS). METHODS: Eighty PCOS patients and sixty-five healthy individuals were enrolled in this retrospective study. Serum levels of miR-205-5p were measured using quantitative reverse transcription polymerase chain reaction (qRT-PCR). The diagnostic efficacy was assessed using receiver operating characteristic (ROC) curves. Logistic regression analysis was conducted to identify the risk factors for insulin resistance (IR) in PCOS patients. Additionally, bioinformatics analysis was performed for the functional enrichment of miR-205-5p targets. RESULTS: Serum levels of miR-205-5p were significantly elevated in PCOS patients, particularly in those with IR (P < 0.001). A high diagnostic accuracy of serum miR-205-5p was displayed for distinguishing PCOS patients from healthy controls (AUC = 0.955) and for distinguishing IR from non-IR among PCOS patients (AUC = 0.852). Moreover, miR-205-5p exhibited a positive correlation with the HOMA-IR value (r = 0.6930, P < 0.001). Abnormal levels of miR-205-5p were significantly associated with BMI, FINS, FBG and HOMA-IR in PCOS patients with IR (all P < 0.001). Furthermore, miR-205-5p was identified as an independent risk factor for IR in PCOS patients, demonstrating a substantial effect size (P = 0.014; OR = 3.849;95%CI = 1.313-11.280), indicating that elevated levels of miR-205-5p were associated with a 3.849-fold increased risk of IR among this population. Bioinformatic analysis and luciferase reporter assays identified SMAD4 as a potential target of miR-205-5p. CONCLUSIONS: MiR-205-5p expression was significantly elevated in PCOS patients with IR, suggesting its potential as a non-invasive biomarker for the early detection of IR in this cohort.