The tailored formulation of raw materials and the combination of grain germination and extrusion processes could be a promising strategy to achieve the desired goal of developing healthier expanded extrudates without compromising sensory properties. In this study, modifications in the nutritional, bioactive profile and physicochemical properties of corn extrudates as influenced by the complete or partial replacement by sprouted quinoa (Chenopodium quinoa Willd) and cañihua (Chenopodium pallidicaule Aellen) were investigated. A simplex centroid mixture design was used to study the effects of formulation on nutritional and physicochemical properties of extrudates, and a desirability function was applied to identify the optimal ingredient ratio in flour blends to achieve desired nutritional, texture and color goals. Partial incorporation of sprouted quinoa flour (SQF) and cañihua flour (SCF) in corn grits (CG)-based extrudates increased phytic acid (PA), total soluble phenolic compounds (TSPC), γ-aminobutyric acid (GABA) and oxygen radical antioxidant activity (ORAC) of the extrudates. Sprouted grain flour usually results in an deleterious effect physicochemical properties of extrudates, but the partial mixture of CG with SQF and SCF circumvented the negative effect of germinated flours, improving technological properties, favoring the expansion index and bulk density and increasing water solubility. Two optimal formulations were identified: 0% CG, 14% SQF and 86% SCF (OPM1) and 24% CG, 17% SQF and 59% SCF (OPM2). The optimized extrudates showed a reduced amount of starch and remarkably higher content of total dietary fiber, protein, lipids, ash, PA, TSPC, GABA and ORAC as compared to those in 100% CG extrudates. During digestion, PA, TSPC, GABA and ORAC showed good stability in physiological conditions. Higher antioxidant activity and amounts of bioaccessible TSPC and GABA were found in OPM1 and OPM2 digestates as compared to those in 100% CG extrudates.