Weight loss in patients with cancer is caused by cancer cachexia and chemotherapy-induced nausea and vomiting. Recent developments in antiemetic drugs have substantially improved nausea and vomiting, but this intervention did not reduce weight loss and other more severe side effects of chemotherapy, like anorexia, weakness, cough, dyspnea, hemoptysis, and pain. This study aimed to investigate the effects of nutrition intervention with a food supplement, during chemotherapy in patients with advanced nonsquamous non-small cell lung cancer (NSCLC). Patients received individualized nutrition counseling by a registered dietitian and were provided with oral supplements of Texidrofolico® for 90 days. Bodyweight and the mentioned other side effects were evaluated at baseline and after 90 days of intervention. To assess the effects of this dietary supplement, a total of 30 patients were retrospectively enrolled as controls, and the bodyweight and change in side effects of chemotherapy were compared with those observed in 30 Texidrofolico®-treated patients. After 90-day intervention, by oral supplement of Texidrofolico®, the patients, during the course of cytotoxic chemotherapy, showed an improved quality of life and not significant weight and BMI loss respect the control group. Furthermore, the number of patients, treated with Texidrofolico® who maintained or increased their body weight, after 90 days of treatment was significantly higher than in the control group. The effects of treatment with the food supplement have also been studied from a metabolic point of view. It was possible to find that one of the known markers of tumor growth, plasma polyamines, was reduced after the treatment. A possible relationship between these biogenic amines and the folate cycle is discussed. In conclusion, early intensive nutrition intervention with oral supplements of Texidrofolico® during chemotherapy of NSCLC patients prevents weight loss and it is beneficial for their quality of life.