Low-gluten diets (LGD) are also widely followed by people not suffering from coeliac disease. This study compared oats and rice as the main cereal source of an LGD in metabolically challenged volunteers. Volunteers (n = 69) were randomly assigned to an LGD, which was either rich in oats or rice, for 6 weeks. Before and after the intervention, concentrations of total cholesterol, LDL-C, and HDL-C, triacylglycerols, free fatty acids, glucose, and insulin were measured from fasting plasma samples; the volunteers also completed 4-day food and stool records, as well as questionnaires related to perceived gastrointestinal discomfort (Gastrointestinal Symptom Rating Scale) and health (RAND-36). The intervention with oats resulted in a more substantial decrease in LDL-C (p = 0.047), more frequently normal type stool (p = 0.010), and bowel movements (p = 0.038) than rice (group × time interaction). The rice group experienced more constipation symptoms (p < 0.001) than the oat group, possibly due to a lower fiber intake (p < 0.001). A greater waist circumference decrease was observed with rice than with oats (p = 0.022). Our results suggest that oats improve both biochemical markers of cardiometabolic health and perceived gastrointestinal well-being compared to rice, thus being a crucial part of a nutritiously adequate LGD.