Acne vulgaris is a common skin inflammatory disease affecting different ages. Antibiotics are the major treatment of acne. Propionibacterium acnes (P. acnes) plays a crucial role in the pathogenesis of acne vulgaris. However, P. acnes has been described to develop antibiotic resistance, which increases our interest in evolving natural antimicrobial compounds that perform complementary antibacterial mechanisms of action to be used in combination with antibiotics in order to decrease resistance and increase the efficacy of the used antibiotics. Honey, vinger and hydrogen peroxide have been reported to have strong antibacterial activities, a few of which were investigated against P. acnes. Hence, the aim of present study was to assess their antibacterial activity on the growth of P. acnes in combination of specific antibiotics, using a checkerboards analysis. Samples were collected from acne lesions of patients and cultured in anaerobic condition to isolate and identify P. acnes, using conventional and molecular methods. Susceptibility tests of the isolated P. acnes were carried out using disc diffusion, Minimum inhibitory concentrations (MICs) using Clinical and Laboratory Standard Institute (CLSI) methods. P. acnes were isolated from 68 out of 186 specimens (36.5%). Resistance of P.acnes isolates to clindamycin is increasing (72.25%), although P. acnes showed susceptibility to a range of antibiotic classes, including beta-lactams, Cephalosporins and carbapenem. Combination of hydrogen peroxide antiseptic with clindamycin showed the highest synergistic activity (83.3%), with a fractional inhibitory concentration index (FICI) of 0.348. Therefore, the combination of hydrogen peroxide and clindamycin has potential activity in treatment of P. acnes.