Background: Small bowel dysbiosis (SBD) is a frequent finding in subjects with irritable bowel syndrome (IBS). The sunflower lecithin (phytosome) formulation of Curcuma longa and Boswellia serrata demonstrated beneficial effects on intestinal microbiota. This study aimed to evaluate the impact of a lecithin-based delivery formulation of Curcuma longa and Boswellia serrata extracts (CUBO) on SBD in IBS subjects. Subjects: Forty-nine adult subjects with IBS and SBD were randomly supplemented for 30 days with CUBO and a low-FODMAP diet (LFD) (intervention) or with LFD and placebo (control group). Results: The intervention group showed a significant reduction in urinary indican (p < 0.001), which was the marker of SBD, and of abdominal bloating (p < 0.001) and abdominal pain (p < 0.001). The pre–post control group analysis did not evidence significant differences. The comparison between the two groups (net effect in intervention minus control subjects) showed that the changes differ significantly for urinary indican p < 0.001 (−42.88; 95% CI: −62.04 to −23.72), abdominal bloating p < 0.001 (−1.50; 95% CI: −1.93 to −1.07), and abdominal pain p < 0.001 (−2.37; 95% CI: −3.61 to −1.13) and for the global assessment of efficacy (p < 0.001). The efficacy was 20% greater in males than in females. Conclusions: In IBS subjects, the intervention with CUBO and LFD shows a significantly higher reduction in SBD, abdominal pain, and bloating compared to LFD and placebo. Additional research is needed to confirm these data.