Background: Smoking is a badly addictive habit due to nicotine contents in tobacco. Shammah is one way of smokeless tobacco that is homely made and it use resulting in multiple medical issues. Aim: The aim of the present study were to chemically analyze the content of various types of Shammah using GC-MS analysis with clinical biochemical investigation of some cases usually used shamma in Makkah region, Saudi Arabia. Methods: Three samples from two main different types of shamma (black and yellow) were collected from local providers and analyzed by Gas Chromatography Mass Spectrometry (GC/MS). Eighteen blood samples were also collected from apparently healthy male peoples (30-45 years) classified into 3 groups; group 1 (control) people who doesn't smoke or use any type of shamma, second and third groups were people who usually used black and yellow shamma respectively; CBC and biochemical analysis were performed. Results: In GC-MS Analysis, the nicotine represents the major constituent in all samples. Total RBCs count, Hemoglobin (HGB) Conc., eosinophil % and iron, total cholesterol, HDL-c concentrations were significantly decreased in peoples using either black or yellow shamma whereas serum levels of ALT, AST and ALP enzyme activities, BUN and creatinine levels were significantly increases. Conclusion: Different shamma samples contains different concentrations of various toxic compounds that can produced a serious health problems as hypochromic anemia due to iron deficiency, decrease in eosinophil %, with hepatic and renal cell injuries detected as increase ALT, AST, ALP, BUN, and creatinine levels.