Sweet potato (Ipomoea batatas L.) is a nutrient-dense tuber often used in traditional diabetic treatment. This research compares the antidiabetic potential of three sweet potato varieties: orange-fleshed (OFSP), purple-peel white-fleshed (PPWSP), and white-peel white-fleshed (WPWSP), utilising in vitro and in vivo techniques. Sweet potatoes (OFSP, PPWSP, and WPWSP) boiled at 100°C for 20 minutes were incorporated into formulated diets and administered to streptozotocin-induced diabetic rats for 14 days. Aqueous extracts of the diets were tested in vitro for antioxidants and phytochemicals. Glycaemic control parameters, lipid profiles, oxidative stress indicators, and pancreatic histology were investigated. Gene expression analysis was performed on critical diabetes-related pathways. OFSP showed significant strong anti-diabetic benefits, including better glycemic control, weight maintenance, lower HOMA-IR scores, and lowered α-amylase and α-glucosidase activity. OFSP-fed rats had higher insulin, glycogen, and hexokinase activity than those given PPWSP and WPWSP. OFSP decreased mRNA expression of DPP-4 while increasing GLP-1 expression. OFSP also improved lipid profiles, increasing HDLc while decreasing LDLc and triglycerides more than other varieties. Histopathological examination revealed restorative effects in pancreatic beta cells. OFSP demonstrated more pronounced antidiabetic effects compared to PPWSP and WPWSP, particularly in terms of glycemic control, insulin regulation, and lipid profile improvement. These findings suggest that OFSP may offer significant potential for diabetes management. However, further clinical studies are needed to validate these results and explore the practical dietary applications of OFSP in diabetes control.