Much of the new research and investigation in pharmacy sciences are concerned with developing therapeutic agents, and identifying and finding new drugs with their chemical structure to treat different human diseases such as infectious diseases from natural products. Therefore, the present findings relate to isolating five new compounds the dichloromethane extract of Peperomia blanda (Jacq.) Kunth grown on Socotra Island, Yemen. two new secolignans; which have been proposed as peperomin I & J. These compounds were isolated together with the other two polyketides presented as surinone D and dindygulerione F. The chemical structures were elucidated and confirmed with nuclear magnetic resonance (NMR) and liquid chromatography-mass spectroscopy (LCMS) analysis. These compounds were first isolated and reported from this plant. These new compounds' antimicrobial activity has been evaluated, and minimum inhibitory concentration has been recorded in the range of 125-250 µg/mL. The pharmacotherapeutic spectrum of compounds was predicated using PASS software which showed potential activity.