Origanum majorana L (Doash) is one of the traditional remedy that is used as a tea and to treat ailments, in the Kingdom of Saudi Arabia. The present study has attempted to evaluate the inhibitory action of Doash fractions on the bioactivation of selected food mutagens and direct-acting mutagens. Four Sallmonella bacterial strains (TA98, TA97, TA100 and TA1530) were used in the present study. These strains contain different mutations in the histidine operon, allowing the bacteria to detect different types of mutation. The two strains (TA98 and TA97) are capable of detecting frameshift mutations, while TA100 and TA1530 are able to detect base-pair substitutions. The liver homogenate and other subcellular fractions were prepared. Identification of Doash fractions was conducted using the high-performance liquid chromatography/mass spectrometry system. The results of the present study demonstrated that the Doash tea fraction components have the ability to reduce the in vitro mutagencity of several promutagens, which were employed in this study. Fraction No. 5 (with the highest content of solid) was the most potent inhibitor of the mutagenicity of all promutagens employed in this study. The antimutagenic effect of Doash tea extract, and its various fractions, was pronounced, indicating that the metabolism of cytochrome P450 1A2 isozyme is likely to be inhibited.