In this study, the effects of goat manure fertilization (2, 4, 8, and 12 Tn/ha) on the grain yield, organic compounds, and mineral composition of two quinoa varieties (CICA-17 and Regalona Baer) were evaluated under field conditions in Northwest Argentina. The results indicate that fertilization improved the quinoa grain yield and total protein content. Low manure doses positively affected the fatty acid (FA) profile, and significant changes were determined for the monounsaturated (MUFA) and polyunsaturated (PUFA) fatty acid contents of CICA-17 and on the saturated fatty acid (SFA) contents of R. Baer seeds. The amino acid contents were positively affected in CICA-17 and negatively in R. Baer. Soluble sugars (glucose, fructose, and sucrose), major elements (K, Si, P, Mg, Ca, and Na), minor elements (Fe, Mn, Al, Zn, and Cu), and ultratrace elements (Cr and Li) were detected and discussed in terms of their impact on human nutrition and health. Conclusively, manure addition affected some essential amino acids, the desaturase activity, the n6:n3 and SFA/UFA ratios, the atherogenic index, soluble sugars, and mineral content, and the fatty acid metabolism of each variety was differently affected, especially the C16 and C18 desaturase activity, which responded differently to various manure doses. Manure addition is a promising alternative to improve the nutritional quality and functionality of quinoa grains, but the response is not linear.