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The unprecedented dissemination of antibiotic resistance announces a close post antibiotic era, thus exploring effective alternatives is urgent. Natural products are untapped alternatives that could offer effective alternatives with low costs. Sparastolonin B (SsnB) is a natural anthracene-derivative with a reported anti-inflammatory activity; however, its potential antibacterial activity is still under-explored. Here, we investigated both antibacterial and anti-inflammatory activity of SsnB in vitro , in vivo and in silico. In vitro, SsnB showed a specific antibacterial activity against Gram-positive bacteria with MIC range of 1–4 µg/ml against S. aureus and E. faecalis . Furthermore, it displayed a profound antibacterial activity against the clinical MRSA strain K15 in both wound infection, and peritonitis infection models with overall bacterial count reductions up to 1.21 and 1.23 log-units respectively. In addition, it has significantly improved wound healing and tissue repair rates compared to the un-treated group in wound infection model. SsnB has also significantly down-regulated the expression of inflammatory mediators, TLR-2, MCP-1, CXCL-1, CXCL-2, IL-6 and IL-1β, in the treated rabbits highlighting its potential anti-inflammatory activity. Finally, in silico analysis has predicted Gyr-B as a potential target for the observed SsnB antibacterial activity. To conclude, SsnB is a promising natural compound with a dual antibacterial and anti-inflammatory activities, suggesting it as a good candidate for subsequent clinical investigation.