Abstract Introduction In vitro and pre-marketing clinical data have shown the healing properties of a postbiotic extract from Aquaphilus dolomiae (ADE-G2). The effectiveness and tolerability of an ADE-G2-based cream were therefore evaluated for the management of minor skin impairment and wound healing in a large population of subjects in routine clinical practice. Methods A real-world, international, pre-post comparative study was conducted in infants, children, and adults with various types of superficial skin impairment who used the study product daily for around 3 weeks according to their dermatologist’s advice. Immediate and follow-up changes in dermatologic signs and symptoms were assessed through clinical scoring. User satisfaction, overall product effectiveness, and tolerability were also evaluated. Analyses were performed in the whole study population and in subject subgroups according to skin impairment type and age. Results Overall, 1317 subjects (83.1% adults, 72.0% female) were included. Dermatologists reported effectiveness and “good” or “very good” tolerability of the cream in 93.8% (1221/1302) and 98.5% (1278/1297) of subjects, respectively. Immediate symptom relief after the first application was reported by 88.3% (849/962) of subjects. After several weeks of regular use (16.7 ± 11.6 days), dermatologic signs and symptoms significantly improved in the whole study population and in the subgroups, with mean decreases in severity scores ranging from –34.5% to –92.5% (p 95%) were “very satisfied” or “satisfied” with the cream and found that skin healing was rapid and of good quality. Conclusion The ADE-G2-based cream proved to be effective and well tolerated in real-life conditions for the management of minor skin impairment in a large and varied cohort of subjects. This product, used as a standalone or adjunctive regimen, can help accelerate the healing of various types of superficial skin impairment.