Background and purpose: Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by beta-cell dysfunction, insulin resistance, and elevated blood sugar levels. Several studies have explored the therapeutic potential of coenzyme Q(10) (CoQ(10)) in managing diabetes, but no reports have examined the possible mechanism of CoQ(10) in T2DM. Here, we reported that CoQ(10) protects pancreatic beta-cell structure and function by modulating the expression of mir-33a/mir-21/SREBP1 and described more detailed tissue alterations. Experimental approach: The study randomly divided rats into three groups (n = 10): control, diabetic, and diabetic + CoQ(10). The diabetic + CoQ(10) group consisted of diabetic rats that were concurrently administered CoQ(10) (20 mg/kg/i.p.) three days/week for eight weeks. In addition to microscopic examination, the study involved evaluating glucose, insulin, and oxidative profiles in the serum and analyzing the levels of cholesterol, mir-33a, mir-2i, and SREBP1 in pancreatic tissue. Findings/Results: Our results revealed that CoQ(10) restores glucose/insulin homeostasis, oxidative parameters, cholesterol levels, and the expressions of mir-33a, mir-21, and SREBP1. In addition, the CoQ(10)-treated diabetic rats showed increased active beta-cells compared to the diabetic group. The immunohistochemical examination of insulin revealed a higher quantity and larger size of pancreatic islets in the experimental group. Conclusion and implications: The restoration of beta-cell integrity following treatment with CoQ(10) may elucidate the therapeutic benefits of this compound in diabetes management, potentially through its influence on the pancreatic expression of mir-33a/mir-21/SREBP1, subsequently maintaining healthy tissue.