Cutibacterium acnes(C. acnes) is involved in the pathogenesis of acne by inducing inflammation and biofilm formation, along with other virulence factors. ACamellia sinensis(C. sinensis) callus lysate is proposed to reduce these effects. The aim of the present work is to study the anti-inflammatory properties of a callus extract fromC. sinensisonC. acnes-stimulated human keratinocytes and the quorum-quenching activities. Keratinocytes were stimulated with thermo-inactivated pathogenicC. acnesand were treated with the herbal lysate (0.25%w/w) to evaluate its anti-inflammatory effect.C. acnesbiofilm was developed in vitro and treated with 2.5 and 5%w/wof the lysate to evaluate quorum sensing and the lipase activity. The results showed that the lysate was able to reduce the production of interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), and C-X-C motif chemokine ligand 1 (CXCL1), and decrease the nuclear translocation of nuclear factor kappa light chain enhancer of activated B cells (NF-κB). The lysate did not show bactericidal activity but showed diminished biofilm formation, the lipase activity, and the production of autoinducer 2 (AI-2), a member of a family of signaling molecules used in quorum sensing. Therefore, the proposed callus lysate could have the potential to reduce acne-related symptoms without the eradication ofC. acnes,which is part of the natural skin microbiome.