eng Enviro Research Publishers Current Research in Nutrition and Food Science Journal 2347-467X 2322-0007 2025-07-10 13 Special Issue Phytonutrients July 2025 179 192 10.12944/CRNFSJ.13.Special-Issue-July.11 23729 article Fazal Hadi 1 Haseeba Sardar 1 Jamelah Saleh Al-Otaibi 2 Abdul Saboor Pirzada 1 Waqas Alam 1 Haroon Khan 3 Department of Pharmacy, Abdul Wali Khan University Mardan, Mardan, Pakistan. 2Department of Chemistry, College of Science, Princess Nourah Bint Abdulrahman University, Riyadh, Kingdom of Saudi Arabia. Department of Pharmacy, Korea University, Sejong, South Korea Diabetes is considered the most prevalent health disorders globally, with its incidence continuing to rise. The available therapeutic are unable to provide adequate hyperglycemic control.  Caralluma edulis has been traditionally consumed as medicine worldwide for managing a range of ailments including diabetes mellitus. The present investigation aimed to analyze the antioxidant and antidiabetic properties of crude hydro-alcoholic extract/ fractions derived from C. edulis. Antioxidant property was determined using ABTS and DPPH methods. In vivo experiments included acute toxicity studies, oral glucose tolerance tests, and streptozotocin-induced antidiabetic activity. The effects on body weight, serum insulin levels, glycosylated hemoglobin, and liver glycogen were also evaluated. Histological analysis of pancreas was also performed. The highest level of antioxidant effect was shown by the ethyl acetate fraction. Oral glucose tolerance test results showed that after 60 and 120 min of glucose loading, there was notable drop in blood glucose levels for the C. edulis extract. The in-vivo antidiabetic investigation showed that crude hydroalcoholic extract at 200 mg/kg had the strongest antidiabetic potential when compared with glibenclamide. The tested medicinal plants led to significant improvement in the body weight, serum insulin, hepatic glycogen, and glycated hemoglobin concentrations. Histopathological analysis showed that the extract considerably reduced the pathological damages, including edema, fatty alterations, vascular congestion, inflammatory infiltrates, and necrosis, in a dose-dependent way. According to our findings, the whole plant of C. edulis demonstrates strong antioxidant activity and holds promising therapeutic potential in diabetes management, as supported by in vitro, in vivo, and histological analysis. https://www.foodandnutritionjournal.org/vol13nospl-issue-phytonutrients-2025/comprehensive-in-vivo-antidiabetic-investigations-and-antioxidant-potential-of-caralluma-edulis-whole-plant/ Antioxidant potential Biochemical analysis Caralluma edulis Histological analysis In vitro antidiabetic