The prevention of hyperglycemia and diabetic complications is essential for diabetes management. Chronic hyperglycemia accelerates the glycation process, increasing advanced glycation end products (AGEs), triggering oxidative stress, and inflammation, thereby causing adverse diabetic complications. Anti-hyperglycemic and antioxidant properties are described for Gynostemma pentaphyllum (GP) and Gymnema inodorum (GI). With the hypothesis that combined therapy may exert better benefits compared to monotherapy, this study aimed to investigate the anti-diabetic and antioxidant activities of combined GP and GI formulas. Plants were extracted with hot water extraction and subjected to testing of anti-α-glucosidase and antioxidant activities, as well as total phenolic content. The extract formula of GP:GI (1:1, w/w) exhibited the highest total phenolic content, and ABTS radical scavenging activity, with values of 4.16 ± 0.21 mg GAE/g extract and 5.06 ± 0.46 mg TE/g extract, respectively. In addition, the combination of GP and GI extracts at ratios of (1:1, w/w) and (2:1, w/w) demonstrated inhibitory activity against α-glucosidase, reducing its activity by 30.40% and 34.04%, respectively. This property was found to be higher, compared to the activity of a single GP or GI treatment at the same concentration. Thus, results indicated that combining aqueous extracts from Gynostemma pentaphyllum and Gymnema inodorum has better antioxidant and anti-diabetic properties. This study supports the use of a combined GP:GI formula as a therapeutic remedy for controlling complications in individuals with hyperglycemia.