Summary: Background: Symptomatic uncomplicated diverticular disease (SUDD) is a chronic condition with a multifactorial pathophysiology involving gut microbiota dysbiosis, impaired intestinal barrier function, and low-grade inflammation. Increasing attention is being given to microbiota-targeted interventions, including probiotics and microbial metabolites such as sodium butyrate. Aim: This study aimed to review current evidence on the role of probiotics and sodium butyrate in SUDD and to present data from a pilot clinical study evaluating a combined intervention. Methods: A narrative review of the recent literature on microbiota modulation, probiotics, and sodium butyrate in diverticular disease was performed. Additionally, results from a prospective pilot study were included, assessing a formulation containing microencapsulated sodium butyrate and four probiotic strains (Lacticaseibacillus rhamnosus, Lactiplantibacillus plantarum, Limosilactobacillus reuteri and Bifidobacterium longum subsp. infantis) in patients with SUDD. Results: Current evidence suggests that probiotics may reduce symptoms in SUDD, although their efficacy is strain-specific and inconsistent across studies. Sodium butyrate exerts anti-inflammatory effects, enhances intestinal barrier integrity, and may reduce abdominal pain independently of gut motility. In the pilot study, significant improvement was observed in most measured clinical symptoms, accompanied by improved quality of life and transient colonization by probiotic strains, supported by sodium butyrate. Microbiome analysis revealed individualized but meaningful shifts toward a more balanced microbial profile. Conclusions: The combination of probiotics and microencapsulated sodium butyrate represents a promising adjunctive strategy in SUDD management, targeting key pathophysiological mechanisms. Further randomized controlled trials are needed to confirm these findings and to define optimal therapeutic protocols.