Triple fixed dose combination product Empagliflozin, Linagliptin and Metformin hydrochloride Extended-Release tablets consists two immediate release agents (Empagliflozin, Linagliptin) and one extended-release agent (Metformin hydrochloride) in a single tablet for the treatment of type 2 diabetes mellitus. The objective of the present study was to optimize process parameters of Empagliflozin, Linagliptin and Metformin hydrochloride Extended-Release tablets using design of experiments. Optimization studies were designed using statistical software (Design expert, stat ease) employing a face cantered central composite design to understand the impact of critical process parameters on responses/dependent variables. Impact of various process variables were assessed by using statistical interpretation such as ANOVA. The selected critical process parameters (fluid uptake and kneading time of high shear granulation process; atomization air pressure and spray rate of fluid bed granulation process) were studied to check the impact on responses/dependent variables (bulk density, %retains on #40 mesh, % passes of #60 mesh). From the obtained results, fluid uptake of 20% w/w, kneading time of 2 min (high shear granulation process); atomization air pressure of 0.9 kg/cm2 and spray rate of 20 g/min (fluid bed granulation process) were selected as optimum process parameters to obtain pre-determined specifications. Keywords: Empagliflozin, Linagliptin, Metformin hydrochloride, Process variables, Design of Experiments, ANOVA.