Aim: The aim of the study was to identify the clinical course and endoscopic activity features in patients with uncomplicated diverticular disease (UDD) associated with diabetes mellitus (DM), overweight, and obesity and perform an analysis of the gut microbiome and morphological characteristics of the colonic mucosa in such patients. Materials and Methods: 259 patients with UDD, hospitalized in the Department of Gastroenterology of Feofaniya Clinical Hospital of the State Administration of Affairs during the period of 2020-2024, were included in the study. Among all patients with DD included in the study, 43 had no metabolic disorders (MD) (DM, overweight, obesity), while 216 presented with varying degrees of MD. All patients underwent total colonoscopy with assessment of endoscopic activity of diverticular inflammation using the Diverticular Inflammation and Complication Assessment (DICA) score. The clinical course of DD was evaluated according to the classification proposed by the German Society of Gastroenterology, Digestive and Metabolic Diseases and the German Society of General and Visceral Surgery in 2021. The microbiome analysis was conducted only in 172 patients who had the financial means to undergo this test. During endoscopic examination of the colon in all patients, mucosal biopsies were obtained from the diverticular orifice. Histological, histochemical, and immunohistochemical methods were used. The obtained digital indicators in the groups were analyzed using statistical methods. Results: This study evaluated clinical, endoscopic, morphological, and microbiological characteristics of DD in patients with metabolic disorders. A recurrent course of diverticular inflammation was observed more frequently in patients with metabolic dysfunctions. Endoscopic assessment of inflammatory activity correlated with histological changes of colon mucosa and alterations in mucin expression (MUC2 and MUC4). Microbiological analysis revealed a reduction in butyrate-producing flora (Akkermansia muciniphila, Faecalibacterium prausnitzii) with predominance of Bacteroidetes in metabolic disorder patients. Conclusions: The clinical, morphological, microbiological and endoscopic features of DD identified by the authors highlight pathophysiological links between metabolic dysfunction (DM, overweight, obesity) and DD progression.