Objectives <p>Many denture-related factors have been identified as risk factors for DS, including trauma, nighttime denture wearing, insufficient oral and denture hygiene. The aim of this research was to examine the effects of local denture factors in the oral mucosa and saliva content that occurred after the DS onset.</p> Materials and methods <p>The study sample comprised 150 adult partial or total denture wearers, 100 of whom were diagnosed with DS, and the remaining 50 had a healthy mucous membrane despite having prosthetic restorations and served as controls. Participants’ saliva was tested for the presence of salivary cytokines (IL-1β, TNF-α, and MMP-9) as indicators of inflammation and damage to the oral mucosa.</p> Results <p>The obtained findings confirmed that local denture-related factors have a major influence on the DS occurrence. Moreover, levels of IL-1β, TNF-α, and MMP-9 inflammatory biomarkers were statistically significantly increased in the DS group.</p> Conclusion <p>A significant DS frequency was noted in denture-wearing patients in whom a large number of local denture factors was present. As inflammation is more prevalent among denture wearers than in general population, regular examinations are advised to facilitate an early diagnosis and implement adequate therapy, with a focus on inflammation and DS prevention.</p> Clinical relevance <p>(1) a greater number of exclusively denture factors can damage the oral mucosa; (2) development of inflammation as a basis for denture stomatitis; (3) increase in the concentration of salivary biomarkers of inflammation; (4) indicates the need for further research regarding the key contributors to the development of DS.</p> Clinical trial number <p>Not applicable.’</p>