Abstract Background Acne vulgaris is a chronic inflammatory dermatosis. Cutibacterium acnes plays a crucial role in the acne pathophysiology. Recent works present evidence of C. acnes growing as a biofilm in cutaneous follicles. This development is currently considered one of the leading causes of C. acnes in vivo persistence and resistance to antimicrobials used to treat acne. Objective Our objective was to evaluate the effects of various active compounds (clindamycin, erythromycin, doxycycline, and myrtle extract) on eight distinct, well‐characterized strains of C. acnes following their growth in biofilm mode. Methods/Results Cutibacterium acnes isolates from phylotypes IA 1 and IA 2 produce more biofilm than other phylotypes. No antibiotic effect was observed either during the curative test or preventive test. Myrtle extract at 0.01% (w/v) showed significant efficacy on the biofilm for C. acnes strains (curative assays). Furthermore, it appear that myrtle extract and doxycycline together reduce the overall biomass of the biofilm. A significant dose‐dependent effect was observed during the preventive test, greater than the one observed under curative conditions, with an important loss of activity of the myrtle extract observed from 0.001% (w/v) concentration onwards. Transmission electron microscopy showed that bacteria treated with myrtle extract grew biofilms much less frequently than untreated bacteria. Additionally, when the quantity of myrtle extract grew, the overall number of bacteria dropped, indicating an additional antibacterial action. Conclusion These findings support the hypothesis that the different C. acnes phylotypes have various aptitudes in forming biofilms. They also suggest that myrtle extract is a promising alternative as an anti‐biofilm and antibacterial agent in fighting diseases caused by planktonic and biofilm C. acnes .