BackgroundOver 85% of teenagers and young adults worldwide suffer from acne vulgaris (AV), a widespread chronic condition that makes up 15%–20% of all skin disease cases. ObjectiveFor AV treatment, 15% Azelaic acid gel has long been promoted as a safe and efficient therapeutic agent. Our goal was to investigate how the skin microbiota of individuals with acne vulgaris was affected by a 15% Azelaic acid gel. Materials and MethodsA total of 55 volunteers who clearly displayed signs of acne vulgaris were recruited. They used a 15% Azelaic acid gel every day for 28 days, with 3 follow-up appointments on the 1st, 14th, and 28th days. The V3–V4 region of the 16S rRNA gene was sequenced to examine the skin microbial samples that were collected. ResultsThe taxonomic makeup of the microbiome communities in acne-affected versus acne-free locations differs significantly. The Alpha and Beta diversity of acne-affected areas improved after 28 days of applying 15% Azelaic acid gel. There were slight decreases in values of Cutibacterium and Staphylococci, which were not statistically significant. Lactobacillus increased considerably (p*=0.01) from 0.97% to 1.60%. Propionibacterium and Staphylococci relative numbers after extended usage of 15% Azelaic acid gel were similar to those of skin not affected by acne. Conclusion15% Azelaic acid gel aided in modifying the skin microbiota within the acne vulgaris group increased the diversity of skin microbiota in the acne-affected area.