Dysgeusia contributes to nutritional derangement and worsens the quality of life of patients with cancer. Despite the different strategies, there is no effective treatment for patients suffering from taste disorders provided by the pharmaceutical industry. We developed a novel strategy for reducing side effects in cancer patients by providing a novel food supplement with the tastemodifying glycoprotein miraculin, which is approved by the European Union, as an adjuvant to medical-nutritional therapy. A pilot randomized, parallel, triple-blind, and placebo-controlled intervention clinical trial was carried out in which 31 malnourished patients with cancer and dysgeusia receiving antineoplastic treatment, and were randomized into three arms: standard dose of DMB (150 mg DMB/tablet), high dose of DMB (300 mg DMB/tablet) or placebo (300 mg freeze-dried strawberry) for three months. Patients consumed a DMB or placebo tablet before each main meal (breakfast, lunch and dinner). Using stool samples from patients with cancer, we analyzed the intestinal microbiome via nanopore methodology. We detected differences in the relative abundances of generaPhocaeicolaandEscherichiadepending on the treatment. Nevertheless, only theSolibaculumgenus was more abundant in the standard-dose DMB group after 3 months. At the species level,Bacteroidessp. PHL 2737 presented a relatively low abundance in both DMB groups, andVescimonas coprocolapresented a relatively high abundance in both treatment groups after 3 months. Furthermore, a standard dose of DMB was positively associated with TNF-α levels andLachnoclostridiumandMediterraneibacterabundances, whereas a high dose of DMB was negatively associated with TNF-α levels and the relative abundance ofPhocaeicola. After a high dose of DMB, erythrocyte polyunsaturated fatty acids were positively correlated withLachnoclostridiumandRoseburia, and there was a positive association betweenPhocaeicolaand the acetic acid concentration of feces. The intake of DMB together with nutritional treatment and individualized dietary advice results in positive changes in the intestinal microbiome of patients with cancer and dysgeusia There was a negative association between the relative abundance ofPhocaeicolaand taste perception in the DMB high dose group. Changes observed in the intestinal microbiota might contribute to maintaining an appropriate immune response of cancer patients. Since the present pilot study involved only a few participants, further research is needed to draw robust conclusions.