Patients with non-celiac gluten sensitivity (NCGS) do not have celiac disease, but their symptoms improve after a gluten-free diet (GFD). However, to date, it is uncertain if gluten or other components of wheat are responsible for these symptoms. The aim of this study was to compare the effects of an organic durum wheat variety with those of standard commercial wheat in patients with known NCGS. We performed a double-blind randomized cross-over trial of 42 patients (mean age 45 years, 8 men) with NCGS diagnosed according to the Salerno criteria and adherence to GFD for at least 12 weeks from screening. Enrolled subjects were randomly assigned to one the following groups of treatment: (A) a two-week diet with Senatore Cappelli wheat variety pasta; (B) a two-week diet with standard commercial pasta. Then, after a two-week washout period on gluten-free diet, each patient crossed over to the other treatment group. Symptoms were assessed through a modified version of the Gastrointestinal Symptom Rating Scale (GSRS), tailored on NCGS. Between April 2018 and July 2018, 42 patients with NCGS were enrolled in the study (70.6% females), and 34 patients completed the study. Patients reported lower overall symptoms scores after eating Senatore Cappelli pasta than standard pasta (p = 0.03) and also significantly lower scores in several specific gastrointestinal and extra-intestinal symptoms after eating Senatore Cappelli pasta than standard pasta, specifically, bloating (p = 0.04), abdominal distention (p = 0.004), eructation (p = 0.01), flatus (p = 0.02), feeling of incomplete evacuation (p = 0.001), dermatitis (p = 0.01), and limb numbness (p = 0.03). In our study, patients with NCGS experienced lower gastrointestinal and extra-intestinal symptom scores after eating the Senatore Cappelli wheat variety than a standard commercial wheat. Should our preliminary results be confirmed by further studies, new dietary alternatives may be available to patients with NCGS, with consequent health, economic, and social benefits.