Durum wheat semolina was fermented with sourdough lactic acid bacteria and fungal proteases aiming at a complete gluten hydrolysis. The gluten-free (GF) semolina, added with naturally GF ingredients and structuring agents, was used to produce bread (rendered GF bread; rGFB) at industrial level. An integrated approach including the characterization of the main chemical, nutritional, structural, and sensory features was used to compare rGFB to a gluten-containing bread and to 5 commercial naturally GF breads. High-performance liquid chromatography was used for free amino acids (FAAs), organic acids, and ethanol analysis. A methanolic extract was used for determining total phenols and antioxidant activity. The bread characterization also included the analysis of dietary fibers, mycotoxins, vitamins, and heavy metals. Beyond chemical analysis, nutritional profile was evaluated considering the in vitro protein digestibility and the predicted glycemic index, while the instrumental texture profile analysis was performed to investigate the structure and the physical/mechanical properties of the baked goods. Beyond the huge potential of market expansion, the main advantages of durum wheat semolina rendered GF can be resumed in the high availability of FAAs, the high protein digestibility, the low starch hydrolysis index, and the better technological properties of bread compared to the commercial GF products currently present on the market. Vitamins, minerals, and dietary fiber profiles are comparable to those of gluten-containing wheat bread. Also the sensory profile, determined by a panel test, can be considered the most similar to those of conventional baked goods, showing all the sourdough bread classic attributes.