The design and formulation of gluten-free breads (GFBs) present challenges in improving nutritional and technological characteristics. The addition of unconventional gluten-free flours has been studied to improve the nutritional profile. The aim of this study was to evaluate the interrelationships of the physicochemical, technological and nutritional characteristics of GFB with the addition of N. affinis flours (NAFs), to comprehensively understand their effect on loaf quality. A traditional GFB recipe was used to replace rice flour and corn starch by fractions of flour obtained from N. affinis grinding (EM: exocarp-mesocarp; ES: endocarp-seed). A Box--Behnken design of three factors [EM, 0-20%; ES, 0-20%; dough water hydration (WH, 70-160%] with three levels (− 1; 0; + 1) was used to obtain the different formulations. Multiple Factor Analysis (MFA) was carried out to correlate instrumental and sensorial data with GFB formulations. The results showed that 72.32% of the data variation was explained by the first two dimensions (F1 and F2). The largest proportion of the variability was explained by F1, where optimal fermentation time, cell size, weight loss, and specific volume were related to WH, discriminating those formulations with higher WH. The latter were negatively correlated to firmness, cell density and uniformity parameters. In F2, EM fraction was correlated to titratable acidity, a*, Chroma and ΔE proteins and dietary fibre content, discriminating between the formulations with a higher proportion of NAF. These formulations were negatively related to carbohydrates, sensorial colour, L*, and pH. The ES fraction was correlated to air inclusion and was used to discriminate the central points of the design. The variables' firmness, cell density and uniformity discriminated the formulations with lower proportions of WH. Through the MFA, it was possible to gain a deeper understanding of the interactions between physicochemical, technological and nutritional properties, and to identify the relevant parameters that affect the quality of GFBs with NAF.