Kañiwa (Chenopodium pallidicaule) and lupine (Lupinus angustifolius) are good gluten-free sources of protein and fiber. The effect of various contents of kañiwa or lupine flour on physical and chemical properties of extruded snacks was investigated. Grain type (kañiwa or lupine), content of kañiwa or lupine flour (20–50% of solids), temperature of die (140–160°C), screw speed (200–500 rpm) and WCM (14–18%) as well as content of protein, ash, fiber and main fatty acids of blend were the predictors in the PLSR model 1. SEI decreased with increasing WCM and content protein and fiber of blend, and increased with increasing screw speed. The stiffness of extrudates containing kañiwa or lupine increased with decreasing screw speed, and increased with increasing WCM, and content of protein and fiber of blend. Extrudates with higher content of kañiwa or lupine presented higher retention of fatty acids and tocopherols while the content of total phenolic compounds and folate was comparable to that of unprocessed flour blends according to PLSR model 2. This study showed that extrudates containing up to 50% kañiwa and at most 20% lupine of solids can maintain high SEI as well as added nutritional value. This study applied successfully PLSR to study the incorporation of kañiwa and lupine to corn-based extrudates. Practical Applications: Up to 50% kañiwa and 20% lupine can be successfully added to expanded corn-based extrudates, thereby increasing the overall content of protein and fiber compared to pure corn extrudates. Extrusion had a minor effect on total phenolic compounds and folate, meaning that some of the nutritional value conferred by kañiwa or lupine was not lost under the conditions tested. Kañiwa, in particular, could have an outstanding potential for the development of gluten-free extruded snacks. Partial Least Squares modeling was a formidable tool to predict the effect of material and process variables on the physical and chemical characteristics of extruded snacks, thus giving valuable information for product development.