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Lactic acid bacteria is well-known as a vital strategy to alleviate or prevent diabetes. Similarly, the plant <i>Saussurea costus</i> (Falc) Lipsch is a preventive power against diabetes. Here, we aimed to determine whether lactic acid bacteria or <i>Saussurea costus</i> is more effective in treating a diabetic rat model in a comparative study manner. An in vivo experiment was conducted to test the therapeutic activity of <i>Lactiplantibacillus plantarum</i> (MW719476.1) and <i>S. costus</i> plants against an alloxan-induced diabetic rat model. Molecular, biochemical, and histological analyses were investigated to evaluate the therapeutic characteristics of different treatments. The high dose of <i>S. costus</i> revealed the best downregulated expression for the <i>IKBKB</i>, <i>IKBKG</i>, <i>NfkB1</i>, <i>IL-17A</i>, <i>IL-6</i>, <i>IL-17F</i>, <i>IL-1β</i>, <i>TNF-α</i>, <i>TRAF6</i>, and <i>MAPK</i> genes compared to <i>Lactiplantibacillus plantarum</i> and the control groups. The downregulation of <i>IKBKB</i> by <i>S. costus</i> could be attributed to dehydrocostus lactone as an active compound with proposed antidiabetic activity. So, we performed another pharmacophore modeling analysis to test the possible interaction between human IkB kinase beta protein and dehydrocostus lactone as an antidiabetic drug. Molecular docking and MD simulation data confirmed the interaction between human IkB kinase beta protein and dehydrocostus lactone as a possible drug. The target genes are important in regulating type 2 diabetes mellitus signaling, lipid and atherosclerosis signaling, NF-κB signaling, and IL-17 signaling pathways. In conclusion, the <i>S. costus</i> plant could be a promising source of novel therapeutic agents for treating diabetes and its complications. Dehydrocostus lactone caused the ameliorative effect of <i>S. costus</i> by its interaction with human IkB kinase beta protein. Further, future studies could be conducted to find the clinical efficacy of dehydrocostus lactone.