Although durum wheat flour is conventionally used to produce pasta, in this study, emphasis was placed on the use of spelt flour in the formulation of the pasta recipe, with the replacement with spent grain obtained from distilleries for its content of fiber and protein. D-optimal design was used to optimize the influence of spent grain addition for the quality attributes of spelt pasta. In order to optimize the spelt pasta matrix, the spent grain content was varied (5%, 10%, 15%, and 20%) so that all responses were optimized (maximize cohesiveness, fracturability, proteins, total dietary fiber, total phenolic content, and antioxidant activity, minimize cooking loss, in-range firmness, and color paste). The optimal addition of spent grain in the spelt pasta recipe was 11.70%, yielding values with differences of less than 5% from the values predicted by the model and producing finished products with good nutritional properties without negative consequences on quality. Spent grain is a valuable byproduct that deserves to be used for fortification in order to obtain pro-health food. This study presents a formulation of spelt pasta with the addition of spent grain using mathematical modeling and statistical optimization.