In the present research volatile organic compounds (VOCs) of garlic/mustard oil macerate (GMM) (garlic clove and mustard oil in the ratio of 1:4, heated at 80 OC for 4 h) was found to enhance the antibacterial activity of antibiotics (gentamycin, 41.17%; kanamycin, 38.89%, and streptomycin, 43.75%) against S. aureus. The mechanism behind the enhancement of S. aureus's sensitivity to antibiotics may be due to reduction of antibiotics resistance. On evaluating one of the well-known antibiotic resistance mechanisms of S. aureus, the ability to produce staphyloxanthin, it has been observed that the VOCs of GMM alone can decrease staphyloxanthin (44.23 ± 0.14%) production. This decrease of staphyloxanthin production and thereby increasing sensitivity to antibiotic, may be assigned to the compounds present in the VOCs of GMM. The major VOCs present in the of GMM were identified as allicin, ajoene, vinyl dithiin, allyl isothiocynate and sinigrin. The order of binding of VOCs with dehydroxysqualene synthase (crtM) protein, which is important in staphyloxanthin production of S. aureus, was found to be sinigrin > ajoene > allicin > dithiin > AITC. Further, decrease in staphyloxanthin production found to increase the membrane fluidity of S. aureus as validated by fourier transformed infrared spectroscopy and scanning electron microscopy and this may allow antibiotics to enter inside the bacterial cell more rapidly.