Caralluma tuberculata N.E.Br. is a naturally occurring plant that has been used for thousands of years for its health benefits. In the present study, the blood sugar lowering effect of C. tuberculata was investigated and compare with that of the diabetes drug metformin. The lyophilized extract of C. tuberculata was administered given to both non-diabetic and diabetic mice. Sixty mice were randomly divided into six groups. Blood glucose levels were measured after 24, 48, 72, and 96 h. The dose was administered orally after being dissolved in maize oil. Analysis of variance (ANOVA) and Tukey’s post hoc test of SPSS were used to determine and compare the hypoglycemic effects of C. tuberculata extract and metformin at different time intervals. In diabetic mice administered C. tuberculata extract at a dosage of 200 mg/kg body weight, there was a significant (p<0.001) decrease in mean blood glucose level and a protective effect on organ weight. When the effects of the drug metformin (150 mg/kg body weight) were compared with those of crude plant extract C. tuberculata, the results indicated that metformin was less effective. C. tuberculate reduced blood glucose levels, and the effect was enhanced when it was combined with maize oil. CTE showed a protective effect against alloxan-induced increases in blood glucose levels and organ weight by increasing insulin production in an in vivo experiment. Therefore, CTE could be a promising pharmaceutical target for the treatment of diabetes.

The study investigated the phytochemical composition, antioxidant activity, antidiabetic efficacy, safety, and organ‐protective potential of Silybum marianum ( S. marianum ) and Citrullus colocynthis ( C. colocynthis ) seed extracts through integrated in vivo and in silico approaches. HPLC analysis identified major bioactive compounds, including gallic acid, caffeic acid, sinapic acid, myricetin, and quercetin. Antioxidant assays demonstrated superior radical scavenging and reducing capacities in S. marianum , which also exhibited higher total phenolic and flavonoid contents than C. colocynthis . Alloxan‐induced diabetic rats were allocated into five groups: normal control, diabetic control, S. marianum ‐treated, C. colocynthis ‐treated, and combined‐treatment groups receiving 250 mg/kg extracts. Treatment significantly reduced blood glucose, improved lipid metabolism, normalized hepatic and renal biomarkers, and enhanced body weight compared with diabetic controls. Histopathological examination revealed restoration of hepatic, and renal architecture, particularly in animals receiving S. marianum or the combined treatment. Acute and subacute toxicity studies demonstrated no mortality or treatment‐related adverse effects up to 5000 mg/kg, indicating a favorable safety profile. Molecular docking further confirmed strong interactions of the identified phytochemicals with α‐amylase, CYP2E1, and GSTA1, supporting their potential mechanisms of action. Overall, these findings demonstrate that S. marianum and C. colocynthis represent safe and promising nutraceutical candidates for the management of diabetes and its associated complications.