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MicroRNA‑146a (miR‑146a) has emerged as a core regulatory molecule in inflammation and metabolism in recent years, and the present review systematically elucidates its critical role and regulatory mechanisms in cardiovascular diseases as well as endocrine and metabolic disorders. Evidence indicates that miR‑146a negatively regulates the nuclear factor‑κB inflammatory signaling pathway by targeting key molecules such as tumor necrosis factor receptor‑associated factor 6 and interleukin‑1 receptor‑associated kinase 1. This regulation impacts various pathophysiological processes, including immune response, inflammatory reactions, oxidative stress, cell apoptosis and proliferation, autophagy, and anti‑fibrosis. The molecule demonstrates a bidirectional dynamic regulatory feature, exhibiting either protective or maladaptive effects in different diseases and stages of disease, particularly in the progression of cardiovascular conditions (such as myocardial ischemia‑reperfusion injury and atherosclerosis) and endocrine and metabolic disorders (such as diabetes and its complications). Additionally, miR‑146a serves as a significant biomarker and therapeutic target. Future research should focus on further elucidating its cell‑ and disease course‑specific mechanisms while promoting the clinical translation of therapeutic strategies based on targeted delivery systems.