Introduction <p>Scalp seborrheic dermatitis (SD) can cause physical discomfort and social embarrassment in affected individuals. Mild-to-moderate scalp SD can be managed using topical products with antifungal, antiinflammatory, and keratolytic properties.</p> Methods <p>A two-phase, randomized, controlled study was conducted to evaluate the clinical efficacy of a newly formulated anti-SD shampoo containing two patented antifungal actives and to investigate the associated changes in the scalp microbiota. The intervention involved a 2-week intensive phase for the 42 subjects included in the study, consisting of the application of the anti-SD shampoo three times a week; a randomized [1:1], controlled, parallel-group 8-week maintenance phase consisting of the test group applying the study shampoo once a week alternately with a neutral shampoo twice a week; and the control group applying the neutral shampoo alone three times a week.</p> Results <p>Following the intensive phase, the scalp condition improved substantially, as evidenced by a significant decrease in the severity of dandruff, erythema, and pruritus, associated with an improvement of SD dysbiosis. These improvements were more sustained in the test group than in the control group during the maintenance phase. The rediversification of the scalp microbiota involved a significant increase in fungal and bacterial richness along with a decrease in the level of SD-predominant <i>Malassezia</i> fungi and <i>Staphylococcus</i> bacteria and an increase in the level of low-abundant fungi genera belonging to the Ascomycota phylum.</p> Conclusions <p>The synergistic effects of antimycotic and antiinflammatory agents in the study shampoo likely contributed to rebalancing the fungal and bacterial ecosystem, thus improving scalp symptoms.</p> ClinicalTrials.gov Identifier <p>NCT06578962 (retrospectively registered on 28 August 2024).</p>