Flavonoids are a class of natural chemicals with variable phenolic structures that have long been recognized for their health advantages, they have recently attracted researchers’ attention for treating diabetes and hyperglycemia. The goal of this research is to develop a novel antihyperglycemic formulation using a combination of three plant flavonoids: Linum usitatissimum L. seeds (FLU), Coriandrum sativum L. seeds (FCS), and Olea europaea var. sylvestris leaves (FOE) based on a mixture design experiment approach which generates the most effective ratio of each component in a mixture instead of the trial-and-error method. Prior to the test, sub-acute toxicity research was conducted to establish a safe and effective dosage. The Oral Glucose Tolerance Test (OGTT) was used to assess the antihyperglycemic impact of these extracts and their combinations in Swiss albino mice. The dose that showed efficacy and safety was 25 mg/kg, which was utilized in all formulations. According to the results, the binary and ternary combinations showed the most significant synergetic effects. The optimum combination with the most potent effect was 37% FLU, 20% FCS, and 43% FOE. This study’s mixture design and prediction model for glycemic variation (GV) may be utilized at an industrial level to develop a novel antidiabetic and antihyperglycemic formulation that is safe and effective.