Recently reports showed that the pathobiology of acne vulgaris was arising from the exploration of sebaceous gland biology, hormonal factors, hyper-keratinization, and the role of bacteria, sebum, nutrition, cytokines and toll-like receptors (TLRs). Propionibacterium acnes (P. acnes) has a strong proinflammatory activity and targets molecules involved in the innate cutaneous immunity on keratinocytes by acting on TLR-2, leads to the development of comedones. GMP, a multi-herb extraction, targeted most of the major pathogenic features of acne with desired physicochemical traits. It strongly suppressed P. acnes growth, and reduced inflammation by suppressing the TLR-2/NF-κB pathway in SZ-95 sebocytes and HaCaT keratinocytes. GMP exhibited a marginal effect on cell viability and may have modulated hyper-keratinization of the epidermis. These results demonstrate the clinical feasibility of applying GMP for the treatment of acne.