Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; AS160, AKT substrate of 160 kDa; Cho, cholesterol; DC, the diabetic control group; D + O200, the diabetic group treated with 200 mg/kg; D + M200, the diabetic group treated with the metformin chemical drug; D + Q50, the diabetic group treated with the 50 mg/kg quercetin; GLUT4, glucose transporter type 4; G6P, glucose 6-phosphate; HDL, High-density lipoprotein; HETEs, hydroxyeicosatctraenoic acid; IRs-1, insulin receptor substrate 1; LDL, low-density lipoprotein; LOX, lipoxygenase; mTORC2, mammalian target of rapamycin complex 2; NC, normal control; okra D + O400, the diabetic group treated with 400 mg/kg okra; PI3K,

Phosphoenolpyruvate carboxykinase (PEPCK) is a key enzyme in the glyconeogenesis pathway. The AMP‐activated protein kinase alpha (AMPK‐α) pathway regulates PEPCK, which itself is activated by the AMP/ATP ratio and liver kinase B1 (KB1). The Abelmoschus esculentus (L.) Moench (okra) plant contains a large amount of quercetin that can function as an agonist or an antagonist. The aim of this study was to examine the effects of quercetin flavonoid and A. esculentus extract on the level of AMPK‐α expression and associated metabolic pathways. The findings demonstrate that metformin, quercetin, and okra extract may significantly raise AMPK‐α levels while significantly lowering PEPCK and hormone‐sensitive lipase (HSL) levels, in addition to improving glucose and lipid profiles. By stimulating KB1, these substances increased AMPK‐α activation. Additionally, AMPK‐α activation improved insulin resistance and Glucose transporter type 4 (GLUT4) gene expression levels. Since AMPK‐α maintains energy balance and its activity has not been reported to be inhibited so far, it could be a potent therapeutic target. Practical applications The development of effective AMPK‐α agonists and antagonists holds promise for the treatment of metabolic disorders like diabetes. Dietary polyphenols are a valuable source for developing new drugs. However, due to the lack of understanding of the underlying mechanisms of their effect on cells, their use in the treatment of diabetes is controversial. In addition to chemicals that have medicinal benefits, chemists are searching for less harmful substances. Using plants containing bioactive chemicals for this purpose can be a good alternative to chemical drugs.