The two-layer tablet of amlodipine and telmisartan is an effective strategy to manage hypertension disease through a combination of various treatment mechanisms. However, the spray-drying method is currently used to prepare telmisartan tablets due to its extremely low solubility, which requires sophisticated equipment. In this study, wet granulation was applied to fabricate this two-layer tablet. Furthermore, design of experiments were deployed to design and optimize the formulation in order to obtain an in-vitro equivalence with the reference drug. As a result, a formulation of the two-layer table using the wet granulation method was successfully developed and optimized. The obtained tablet showed an in-vitro equivalence with the reference drug (with f2 superior to 50 for both amlodipine and telmisartan). Furthermore, the obtained tablet also met a set of in-house standards, including appearance, identification, assay, and dissolution rate. This study provided not a novel but effective and simple method of fabrication for amlodipine-telmisartan tablets using wet granulation. Furthermore, the obtained results also highlighted the significant contribution of a well-established design of experiments in the development of a complex tablet formulation.