A mixture design (MD) was used to evaluate the effect of replacing wheat flour (WF) with sprouted cañihua (Chenopodium pallidicaule Aellen), kiwicha (Amarathus caudatus L.), and quinoa (Chenopodium quinoa Willd.) flours (SCF, SKF, and SQF, respectively) on the content of phytic acid (PA), γ-aminobutyric acid (GABA), total soluble phenolic compounds (TSPC), and antioxidant activity (AA) in biscuits. Generally, sprouted pseudocereal flours contained lower amounts of starch and protein, comparable fat, ash, PA content, and increased levels of bioactive compounds (GABA and TSPC) and AA compared with wholegrain flours. Moreover, it was confirmed that sprouted pseudocereal flours were nutritionally superior to refined WF. MD allowed the modeling of target parameters showing that PA, GABA, TSPC, and AA were positively influenced by the proportion of flours in the biscuit. The models that better described the variation in nutritional parameters as a function of the formulation displayed typically linear and binary interactions terms. SKF exerted the highest influence on the increased content of PA. Therefore, to increase mineral bioavailability, the use of SCF and SQF in the formulation of biscuits was suggested. SCF and SQF positively influenced in GABA, TSPC, and AA in biscuits. The optimal ternary blends of flours that maximize the content of bioactive compounds and AA of biscuits and simultaneously minimize PA content were identified. To study the fate of biscuits in digestion, the optimal formulation for biscuits containing SQF/SCF was selected. For this type of baked product, reduced starch digestibility and glycemic index was observed compared with the control (100% WF). Moreover, the amounts of bioaccessible GABA, TSPC, and AA were higher in gastric and intestinal digests compared with control biscuit. Overall, these results highlighted the nutritional and health benefits of incorporation of flours from sprouted Andean grains in the production of biscuits.