An imbalanced gut microbiota predisposes the development of nutritional disorders and chronic gastrointestinal diseases. Several studies have shown improvements on the host's health by enhancing the microbiota with prebiotics that stimulate probiotic microorganisms. This study describes the prebiotic effect of fructans from Agave salmiana consumed by children as a supplement for malnutrition. We report the extraction and degree of polymerization of fructans from A. salmiana, food safety and inflammatory analyses, and their effect in vitro on probiotic lactic acid bacteria (LAB). These fructans were included in the diet of 5-year-old normal-weight and malnourished children in double-blind, two-week interventions that compared the effects on their weight, bacterial count, and volatile organic compounds (VOCs). The extracted powdered fructans from A. salmiana had a composition comparable to inulin, were safe for human consumption, and stimulated the growth in vitro of three characteristic LAB. The children who consumed these fructans had a considerable weight gain, an increased number of LAB, and a decreased concentration of VOCs (indicative of less dysbiosis), demonstrating positive effects of this prebiotic on their microbiota, which were more significant in malnourished children. Fructans from A. salmiana induced in malnourished children significant weight gain and improved the functionality of their gut microbiota.