Background Acne vulgaris is a common skin disease characterized by increased sebum production, inflammation, and colonization of Propionibacterium acnes (P. acnes) on pilosebaceous follicles. Aims To determine the efficacy of two different plant extracts against P. acnes and to analyze the gene expression levels of IL-1 alpha, SRD5A1, and TNF alpha in HaCaT cells treated with these plant extracts. Methods Anti-acne extract 1 (AE1) consisted of Juglans regia (walnut husk), Myrtus communis (myrtle leaves), Matricaria chamomilla (chamomilla flowers), Urtica dioica (stinging nettle leaves), and Rosa damascena (rose flowers). Anti-acne extract 2 (AE2) contained Brassica oleracea var. botrytis (broccoli) and B. oleracea var. italica (cauliflower). The antimicrobial activities of the extracts were tested on two different P. acnes strains: the reference strain of P. acnes (ATCC 51277) and the clinical isolate from a patient. The minimum inhibitory concentration (MIC) of the extracts was determined using the broth dilution method. Human keratinocyte cells were used for in vitro tests. Gene expression analyses were performed with RT-qPCR. Results The MIC values of the extracts were below 1/2048 mu g/mL. In the gene expression analysis, AE1 increased the expression level of TNF alpha (1.1719, P < 0.0001), suppressed the expression level of IL-1 alpha, SRD5A1 (0.0588, P = 0.0231; 0.3081, P = 0.0351), respectively. AE2 suppressed gene expression level of IL-1 alpha, SRD5A1, TNF alpha (0.3815, P = 0.0254; 0.3418, P = 0.0271; 0.1997, P = 0.0623). Conclusions Both herbal extracts demonstrated strong antibacterial and anti-inflammatory activity in this preliminary trial. In conclusion, the topical application of these botanical extracts can be good candidates for local acne treatment.