Lactic acid bacteria is well-known as a vital strategy to alleviate or prevent diabetes. Similarly, the plantSaussurea costus(Falc) Lipsch is a preventive power against diabetes. Here, we aimed to determine whether lactic acid bacteria orSaussurea costusis more effective in treating a diabetic rat model in a comparative study manner. An in vivo experiment was conducted to test the therapeutic activity ofLactiplantibacillus plantarum(MW719476.1) andS. costusplants 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 ofS. costusrevealed the best downregulated expression for theIKBKB,IKBKG,NfkB1,IL-17A,IL-6,IL-17F,IL-1β,TNF-α,TRAF6, andMAPKgenes compared toLactiplantibacillus plantarumand the control groups. The downregulation ofIKBKBbyS. costuscould 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, theS. costusplant could be a promising source of novel therapeutic agents for treating diabetes and its complications. Dehydrocostus lactone caused the ameliorative effect ofS. costusby its interaction with human IkB kinase beta protein. Further, future studies could be conducted to find the clinical efficacy of dehydrocostus lactone.