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Quinoa and amaranth are of special interest since they are increasingly used for the development of new bakery products with enhanced nutritional value. The aim of the study was to evaluate the agronomic, microbiological, and nutritional characteristics of quinoa and amaranth seeds grown in Southern Italy. For this reason, quinoa Titicaca and three amaranth accessions (5, 12, and 14) were cultivated in different experimental fields in the Campania Region and analyzed for the cultivation aspects, chemical composition, and microbiological quality of the seeds. All seeds showed a good adaptability to cultivation in the experimental areas of the Mediterranean basin. Quinoa seeds were characterized by their higher protein, fat, and ash content than the amaranth seeds, which were characterized by their higher value in dietary fiber. All seeds, regardless of the geographical area of production, were contaminated with yeasts, moulds, and spore-forming bacteria, mainly Bacillus cereus, B. licheniformis, B. safensis and B. subtilis, as identified by 16S rRNA sequencing analysis. So, the detection of Bacillus spp. must be strongly monitored, as quinoa and amaranth seeds could be used in bread production, where they can cause ropiness, resulting in great economic losses for the industries.