Intensive studies on extracts and biologically active compounds isolated from medicinal plants have doubled in the last decade worldwide. However, as a result of paucity of knowledge and folkloric claim on the effectiveness of sesame leaves in infectious disease treatments, we aimed to determine the synergistic antimicrobial activity of essential oils and lignans present in the crude leaves extracts of
Sesame radiatum
and
Sesame indicum
. Ethanolic, methanolic and aqueous extracts of both leaves were studied for their in-vitro synergistic antimicrobial activity against both Gram positive and Gram negative micro-organisms, and Yeast using Agar diffusion method. The GC-MS phytochemical screening of methanolic extract showed that the major compounds in essential oils are of carboxylic acids and phenolic groups especially, the most potent antioxidants known to man like sesamol, sesamolin and sesamin among others. Methanolic and ethanolic extracts have broad spectrum antimicrobial effect against all the tested pathogenic micro-organisms except
Streptococcus pneumoniae
and
Staphylococcus aureus
respectively, while the aqueous extract exhibited inhibitory activity on
Staphylococcus aureus,
Streptococcus pneumoniae and
Candida albicans
. The result confirmed the folkloric claims of the antimicrobial effectiveness of locally consumed sesame leaves extracts especially against bacterial and common skin infection in many areas of Nigeria .